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11th Conference on Retroviruses and Opportunistic InfectionsSan Francisco, Califonria - February 8 - 11, 2004 |
Cite as: Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. xx)
| 2 | Multinational Business Responding to AIDS in South Africa Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 2) Gavin Churchyard1, S Charalambous1, A D Grant2, L Pemba1, D Martin3, R Wood4, J Sim3, R Chaisson4, and B A Brink5 The availability of ART has not stimulated a large increase in demand for VCT. In centers where capacity for rapid enrolment into the ART program exists, enrolment has been slower than anticipated. Obstacles to enrolment for ART need to be identified and addressed. This program provides a model for ART delivery in industrial settings in Africa. |
| 3 | Scaling up HIV Testing for a Global Response to HIV/AIDS Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 3) David Miller This presentation will provide field-based data and experiences informing the scaling up of T&C on a global scale, address some of the key challenges to these processes, and describe the WHO approach to increasing access to T&C services. |
| 4 | The Ugandan Experience in Scaling up HIV/AIDS Treatment and Care Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11: (abstract No. 4) Alex Coutinho1, P Mugyenyi2, and P Solberg3 There are particular challenges in scaling up ARV use in a resource-challenged setting, and this presentation explores those challenges while highlighting the successes of current efforts. The presentation will also discuss the role of the partnership between government, NGO, and the private sector in this scale up. |
| 5 | HIV/AIDS in Thailand: Factors that Make Differences Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11: (abstract No. 5) Anupong Chitwarakorn Despite the substantial progress Thailand has made in its HIV/AIDS program, it still needs to improve the prevention effort to further reduce the incidence and alleviate the burden of people living with HIV/AIDS. Some challenges are to maintain and strengthen national sexually transmitted diseases (STD) prevention and control program, focusing on 100% condom use, behavior intervention and effective diagnosis and treatment; to initiate and strengthen effective prevention program among injecting drug users; to ensure increase the access to medical care for HIV/AIDS patients including ARV drugs; to expand, mutisectoral partnership in the design, implementation, and evaluation of HIV/AIDS-related policies and program; and to promote research which will provide valuable information on the factors influencing the epidemic and its effective counter measure. |
| 6 | Cellular Factors and HIV Budding Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 6) Wesley I Sundquist Thus, HIV release and MVB biogenesis appear to be analogous processes. I will discuss our ongoing biochemical and structural studies of protein complexes along the MVB pathway and the generality of this pathway for virus release. |
| 8 | Molecular Virology and Pathogenesis of Hepatitis C Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 8) Charles M Rice Although these are powerful systems, concern remains that they may not truly represent replication in vivo. For example, replication of HCV RNA in cell culture often requires adaptive mutations in the replicase that are deleterious for replication in vivo. Nonetheless, proof-of-concept data are emerging for compounds with potent replicon inhibition in cell culture that are also highly effective in vivo. While these results are encouraging, continued efforts are needed to develop replicons for other HCV genotypes, complete infection systems, and animal models to assess in vivo efficacy and emergence of resistance. On the vaccine front, despite early pessimism, evidence is emerging for protective immunity in resolved natural infections and in experimental prophylactic vaccines tested in chimpanzees. |
| 9 | How Close Are We to an Effective Microbicide? Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11: (abstract No. 9) Robin J Shattock This presentation will discuss how our increasing knowledge of the ways in which HIV-1 is transmitted is shaping the development of new, more sophisticated intervention strategies based on the application of vaginal or rectal microbicides, the major hurdles in the development of different biologic approaches and likely timescales for providing an effective microbicide to protect those most at risk of infection. |
| 10 | Gag-specific T Helper and CTL Responses Are Associated with Effective Control of HIV C Clade Infection in Durban, South Africa Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11: (abstract No. 10) D Ramduth1, P Chetty1, N Ntumba1, S Gappoo1, J Harlow1, C Henry1, I Honeyborne1, P Jeena1, M M Addo2, M Altfeld2, C Brander2, P Kiepiela1, B D Walker2,3, and P J R Goulder4 These data demonstrate a strong and consistent association between the magnitude of the CD4+ IFN-γ response and the CD8+ response. The T helper response is dominated by the Gag specificity. The Gag-specific CD8+ T-cell response showed a strong negative association with viral load. The opposite trends were observed for CD4+ and CD8+ T-cell responses to HIV proteins other than Gag. These results suggest that overall Gag-specific CTL epitopes are valuable for control of HIV C-clade infection and underline the importance of Gag-specific T-helper responses in the maintenance of the CTL response. |
| 11 | Immunological and Genetic Determinants in HIV-1 Controllers and Long-term Non-progressors. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 11) M M Addo1, A Rathod1, R Draenert1, D Kaufmann1, M R Perkins1, C Verrill1, M N Johnston1, A G Wurcel1, C Corcoran1, J Braun2, M Altfeld1, S K Kalams3, S Buchbinder4, E S Rosenberg1, B D Walker1, and The HIV-1 controller study group Robust CD8 T-cell responses can be detected in both HIV-1 controllers and progressors. Our data suggest that HIV-1-specific CD8 T cells of mature phenotype may be more easily detectable HIV controllers. A high proportion of individuals expressed HLA class I alleles associated with slow disease progression, indicating that control of viral replication may be at least partially CD8+ T-cell mediated, but others had weak to undetectable responses. These data indicate that viral controllers are a heterogeneous group, and that multiple factors may influence long-term containment of viremia. |
| 12 | Comparison of CD8 T-Cell Responses and Viral Escape in HIV-infected Monozygotic Twins. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 12) R Draenert1, T M Allen1, G Sirera2, C L Verrill1, R Eldridge1, L Ruiz2, B D Walker1, and J Martinez-Picado2 This setting shows that although the majority of CD8 T-cell responses are similar, with viral escape developing in parallel, responses and viral evolution differ. This implies that the genetic background is a major determinate for CD8 T-cell responses, but other factors play a role as well. These results are important for understanding HIV pathogenesis and for vaccine development. |
| 13 | Selection, Transmission, and Reversion of an Antigen Processing CTL Escape Mutation in HIV-1. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 13) T M Allen*1, M Altfeld1, X G Yu1, K M O'Sullivan1, M Lichterfeld1, P K Lee1, S Le Gall1, B R Mothe2, D E Cohen3, K A Freedberg1, A Sette4, E S Rosenberg1, P J R Goulder5, C Brander1, and B D Walker1 These data reveal an additional mechanism for HIV-1 to evade host immune responses and the effect of transmission of CD8 escape mutations on mounting of acute-phase responses. Reversion of a transmitted CD8 escape mutation suggests that some frequently occurring CD8 epitopes are not destined to be lost within the population, and implies a potential fitness cost to the virus from the mutation. A better understanding of these selective forces will be important for design of intracellularly processed HIV-1 vaccines. |
| 14 | CD4+CD25+ Regulatory T-like Cells Suppress HIV-specific CD4+ and CD8+ T Cell Immune Responses in vitro. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 14) A Kinter*1, M Hennessey1, A Bell1, Y Lin1, R Jackson1, M Planta1, M McLaughlin1, S Zeigler2, and A S Fauci1 These data demonstrate that a subset of CD25+CD4+ T cells isolated from HIV-infected donors exhibit a CD25+CD4+ Treg-like phenotype and suppress HIV-specific immune responses in vitro. These findings suggest that CD25+CD4+ Treg-mediated immunosuppression may restrict the ability of both CD4+ and CD8+ T cells to effectively control HIV replication in vivo. |
| 15 | Functional and Phenotypic Heterogeneity of Memory CD4 T Cells Are Dictated by Antigen Persistence and Load. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 15) A Harari, F Vallelian, S C Zimmerli, and G Pantaleo Antigen persistence and antigen load appear to influence substantially the composition of functional and phenotypically distinct CD4 cell populations in different models of immune response. |
| 16 | Substantial discrepancies between cytotoxic activity and interferon-gamma secretion of HIV-specific CD8+ T cells. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 16) M Lichterfeld*, X G Yu, D Kaufmann, S Mui, N Johnston, D Cohen, M M Addo, D Strick, E S Rosenberg, B D Walker, and M Altfeld These results suggest that the direct cytolytic effects of HIV-specific CD8+ T cells are preferentially mediated by the subset of cells capable of producing both interferon-γ and TNF-α in response to viral stimulation. The characterization of this CD8+ T cell subset will be thus relevant for a more precise evaluation of CD8+ T cell mediated HIV-specific immune responses generated naturally or following immunization with HIV vaccine candidates. |
| 17 | Infection with HIV-1 Leads to Up-regulation of HLA-E Expression Resulting in Impaired Cytotoxic Function of Natural Killer Cells. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 17) J Nattermann1, H D Nischalke1, V Hofmeister2, B Kupfer1, G Ahlenstiel1, G Feldmann1, J Rockstroh1, E Weiß2, T Sauerbruch1, U Spengler1, and BMBF, Kompetenznetz HIV/AIDS In conclusion, these results propose HIV-mediated up-regulation of HLA-E expression as an efficient evasion strategy targeting the antiviral activities of NK cells and allowing the virus to establish itself as a chronic infection. |
| 18 | Stoichiometry of neutralization of HIV-1 primary isolate JR-CSF by anti-gp120 antibodies. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 18) M Franti1, S Frost2, M Guyader1, K Delgado1, D R Burton1, and P Poignard1 Results suggest that the stoichiometry of neutralization of HIV-1 primary isolates follows a multiple hit kinetic, is incremental, and may result not only directly from monoclonal antibody-mediated blocking of bound envelope trimers, but also indirectly, from decreasing the rate of productive interaction with the target cell. Different stoichiometries may arise from different modifications by the monoclonal antibody to the rate of productive virus-cell interaction. |
| 19 | Neutralizing Antibody Responses Often Persist at High Titers in Chronic HIV Infection but Do Not Exert an Antiviral Effect Against Autologous Virus. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 19) S Deeks1, T Wrin2, J Galovich2, J Martin1, and C Petropoulos2 Chronic HIV infection is associated with high levels of neutralizing antibody responses that appears not to be directed at autologous virus, and is therefore unlikely to be contributing to virologic control. In contrast to observations made during acute HIV infection, there was only limited evidence that HIV continued to develop novel escape mutations. These data indicate that HIV replication in chronic disease drives the production of high amounts of ineffective HIV-specific antibodies and that the capacity of the immune system to continuously generate antibodies directed at emerging epitopes within HIV envelope is eventually exhausted. |
| 20 | The "Screening and Tracing Active Transmission" Program: Real-time Detection and Monitoring of HIV Incidence Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 20) C Pilcher1, E Foust2, J McPherson2, R Ashby2, J Owen-O'Dowd2, T Nguyen1, R Lee2, S Fiscus1, and P Leone1 With HIV VCT enhanced by NAT, public helath programs can actively monitor HIV transmission in populations by identifying incident infections in real-time. The additional cases identified by NAT are those with maximm potential for secondary spread. The Screening and Tracing Active Transmission (STAT) program is a new model for increasing effectiveness of VCT-based HIV surveillance and prevention programs. |
| 21 | Incidence of HIV Superinfection Following Primary Infection Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11: (abstract No. 21) D Smith1, J Wong1, G Hightower1, K Kolesch1, C Ignacio1, E Daar2, D Richman1,3, and S Little1 While initial co-infection cannot be ruled out, 4 independent lines of molecular investigation provide compelling evidence that these are cases of HIV-1 clade-B superinfection. Since population-based pol sequencing is a conservative screening method, this may underestimate the true superinfection rate. Other cases may have been missed if the superinfecting strain was a minor variant below the level of detection, or if the superinfecting strain replaced its original pol gene with the initial HIV strain's pol gene through recombination. Harm reduction counseling with patients is essential even if their risk exposures are with other HIV-infected people, as superinfection could have detrimental clinical consequences by accelerating disease progression and limiting future treatment options. |
| 22 | Autologous Neutralizing Antibody Responses Drive the Evolution of HIV-1 env in Recently Infected Patients Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11: (abstract No. 22) S D W Frost1, T Wrin2, E Paxinos2, C Chappey2, J Galovich2, J Beauchaine2, C J Petropoulos2, S J Little1, and D D Richman1,3 Our data suggest that the evolution of env is driven by neutralizing antibody responses. Viral escape may account for the plateauing of neutralizing antibody responses to baseline virus. Heterologous neutralizing antibody responses may be mediated differently than autologous neutralizing antibody responses, as shown by the lack of correlation between genetic distance and heterologous neutralization, and the continued increase of heterologous responses over time since infection. |
| 23 | Effect of Treatment during versus after Acute Retroviral Syndrome (ARS) on HIV Viral Load and CD4 Cell Counts within 3 Years of Infection Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11: (abstract No. 23) N Voirin1, D Smith2, J P Routy3, M Legault3, D Baratin4, C Trepo1,5, L Cotte5, J M Livrozet4, J L Touraine4, D A Cooper2, A Gayet-Ageron4, J Ritter4, J Fabry4, and P Vanhems1,4 We observed no beneficial effect of early initiation of therapy on HIV viral load and CD4 cells count over the next 3 years. This suggests that any delay in starting therapy may have only minor effect at 3 years on CD4 cells count and HIV RNA, after taking HAART effectiveness into account. These observational data do not support the urgent initiation of ART in patients with ARS, but randomized clinical trials are needed to conclude. |
| 24 | Limited Durability of Immune Control following Treated Acute HIV Infection Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 24) D Kaufmann1, M Lichterfeld1, M Altfeld1, T Allen1, M Johnston1, P Lee1, B Wagner1, E Kalife1, D Strick1, E Rosenberg 1 and B D Walker1,2 These data indicate that despite initial control of viremia, durable immune control in persons following treated acute infection occurs infrequently, and that larger trials will be needed to determine the potential clinical and virologic benefit of this approach. Loss of viremia control occurred in some individuals despite increase of the magnitude of HIV-specific CD8 T-cell responses during the first supervised treatment interruption. These data are relevant to current efforts to develop an AIDS vaccine designed to retard disease progression rather than prevent infection, and indicate that durable maintenance of low level viremia may be difficult to achieve. |
| 25 | Selection of Breakthrough HIV-1 Infection in Long-term Exposed Seronegative Individuals Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11: (abstract No. 25) T Zhu1, R Zinoi1, H Zhu1, Y Xu1, J Lee2, P Nelson2, T Andrus1, N Llwellyn1, H Liu1, D Nickle1, Y Hwangbo1, J Mullins1, L Corey1, and J McElrath2 These findings indicate that breakthrough HIV-1 strains in exposed seronegatives/late seroconverters tends to be divergent from those of their long-term sexual partners, suggesting that continued virus exposures might protect partner-like HIV-1, but allow distinct viral strains to infect. Pre-infection CTL responses might play an important role in the positive selection of breakthrough HIV-1 infection in late seroconverters. |
| 26 | Hepatitis C and Neuropsychological Function In Treatment Naïve HIV-1-infected Subjects - A5097s Baseline Analysis Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11: (abstract No. 26) Y Yang1, S Evans1, R Gulick2, D Clifford*3, and AIDS Clinical Trials Group A5097s Team Our findings suggest that HCV/HIV co-infection adversely affected neuropsychological performance, particularly in the Digit Symbol task. HCV may also be associated with depressed mood particularly with somatic complaint. Despite a limited sample size and the difficulty of excluding all possible confounding factors, our results control for many potential confounds while still demonstrating a probable effect of hepatitis C on neuropsychological performance. |
| 27 | Risk Factors and Determinants for HIV-associated Sensory Neuropathies: Is Hepatitis C a Modifier? Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11: (abstract No. 27) J C McArthur1, J Creighton1, R Skolasky1, L Lal2, R Moore1, K Carter1, S Wesselingh2,4, K Cherry2,4, and Johns Hopkins Neuroscience Group The frequency of asymptomatic and symptomatic sensory neuropathies was remarkably high at both sites, with only 32% of subjects neuropathy-free at baseline. Hepatitis C serostatus did not appear to influence the prevalence of SN at baseline, however, longitudinal study will disclose its modifier role. Morphological abnormalities were noted in a high proportion of neuropathy-free subjects, and longitudinal follow-up may disclose a high transition rate to confirmed neuropathy. |
| 28 | CCR2 Polymorphisms Affect Neuropsychological Impairment in HIV-1-infected Adults. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 28) K Singh1, R Ellis2, J Marquie-Beck2, S Letendre2, R Heaton2, I Grant2, and S A Spector1 A genetic variant of CCR2 (V64I), the principal receptor for the chemokine MCP-1, was associated with more rapid progression to neuropsychological impairment in this cohort of HIV-infected adults. The CCR2 polymorphism was not associated with increases in plasma or CSF viral load, suggesting that the impact of CCR2 on neuropathogenesis may involve alterations in host immune responses within the CNS rather than a direct impact on viral entry and replication. |
| 29 | Chemokines Correlate with Cerebral Metabolites on Magnetic Resonance Spectroscopy: A Substudy of ACTG 301 and 700. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 29) S Letendre1, J Zheng2, C Yiannoutsos3, A Lopez2, R Ellis1, J Marquie-Beck1, J Zimmerman1, H Gendelman2, B Navia4, and The ACTG 301 and 700 Study Teams Chemokines predict changes in neuropsychological performance and reflect cerebral metabolites, further implicating them in HIV neuropathogenesis. In this study, chemokines were associated with NAA, a marker of neuronal integrity, and choline, a marker of gliosis, in parietal cortex. |
| 30 | Changes in the Quantitative Neurological Performance Z Score on 4 Tests n an HIV-1-infected Cohort: Association with CSF HIV Concentration and Changes in Blood T Cells. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 30) A Nilsson, K Onstott, S Spudich, D Verotta, S Deeks, and R Price Overall, neurological function in the cohort, as assessed by the QNPZ-4 score, improved slightly over 1 year without a clear difference among the 3 groups. However, the course of HIV infection (as indicated by CSF HIV concentrations at 1 year and changes in T-cell counts) was associated with changes in neurological performance across the entire cohort. |
| 31 | Evidence for HIV-1 Infection of Neural Progenitor Cells. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 31) Lawrence D, Schwartz L, Durham L, Major E; NINDS, NIH, DHHS, Bethesda, MD, USA Periventricular colocalization of HIV-1 and nestin in archival pediatric brain, combined with infection of human neural progenitor cells in culture, support the idea that neural progenitor cells may harbor HIV-1. Differentiation into an astrocytic phenotype is associated with higher viral titer, as is stimulation with TNFα. Progenitor cells might be an additional reservoir of HIV-1 in the pediatric brain. |
| 32 | HIV-1-mediated Apoptosis of Neurons: The Proximal Mechanisms of HIV-1-Induced Encephalopathy. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 32) R Pomerantz, Y Xu, J Sullivan, and J Kulkosky These data suggest that the exposure of neurons to viral products may be more critical for the induction of apoptosis relative to putative host factors released from the virally infected cells, and denote direct molecular mechanisms for the induction of apoptosis in neurons relating to the exposure of viral and host cell factors. As such, relevant rationally designed targets can now begin to be designed for interdicting in HIV-1-induced neuronal cell loss. |
| 33LB | Progressive White Matter Loss Suggests Ongoing Brain Injury in ART-treated HIV+ Patients Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 33LB) M W Weiner1, D J Meyerhoff1, V Cardenas-Nicolson1, J Kornak1, C Studholme1, D Truran1, J Rothlind1, L Chao1, H Lampiris1, R Grant4, and J Lindgren1 Prior to ART, the CNS was a major target of HIV, often producing dementia. Since introduction of ART, CNS complications of HIV have been much less severe. Nevertheless, there has been concern that CNS injury may occur despite ART treatment. Therefore, the goal of this longitudinal study was to test the hypothesis of ongoing CNS injury in both light drinking (LD) and heavy drinking (HD) ART-treated HIV+ subjects compared with HIV- controls. |
| 34 | Peripheral Neuropathy Associated with HIV and ARV: Update on Diagnosis and Management Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 34) David M Simpson*1 and J C McArthur 2 1 Mount Sinai Med Ctr, New York, NY, USA and 2 Johns Hopkins Sch of Med, Baltimore, MD, USA BACKGROUND: More than one third of patients with HIV/AIDS have peripheral neuropathy . However, peripheral neuropathy is frequently misdiagnosed, particularly by non-neurological clinicians. Recent cohort studies have provided data on the reliability of brief screening batteries in the diagnosis of neuropathy, in compa |
| 35LB | Continuing High-risk Sexual Behavior and Increasing Antiretroviral Resistance among HIV+ Patients in Care Helps Explain the Rising Prevalence of Resistance among New HIV Infections Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11: (abstract No. 35LB) Kozal M, Amico R, Chiarella J, Schreibman T, Cornman D, Fisher W, Fisher J, Friedland G; Yale Univ. Sch. of Med., New Haven, CT, USA BACKGROUND: The prevalence of drug resistance among new HIV infections is increasing. The presumed source of new resistant infections is HIV+ patients receiving antiretroviral therapy (ART) who engage in behaviors that transmit HIV. Little is known about the risk behaviors of these patients, potential partners exposed |
| 36LB | Persistence of Transmitted Drug-resistant Virus among Subjects with Primary HIV Infection Deferring Antiretroviral Therapy Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 36LB) S J Little*1, K K Koelsch1, C C Ignacio1, J K Wong1,2, Y Lie3, S D W Frost1, and D D Richman1,2 1Univ. of California, San Diego, La Jolla, USA; 2San Diego VA Healthcare System, La Jolla, CA, USA; and 3ViroLogic, Inc., South San Francisco, CA, USA BACKGROUND: We wanted to assess the persistence of transmitted drug resistant variants in the absence of antiretroviral drug (ARV) treatment among subjects with primary HIV infection. METHODS: Baseline nucleotide sequence analysis of pol was used to identify major drug-resistance mutations among 11 subjects with primar |
| 37 | Emergence and Long-term Persistence of NNRTI-resistant Variants in Patients Starting and Stopping NNRTI-containing Regimens Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 37) S Palmer*1, V Boltz1, F Maldarelli1, E Halvas2, J Mican3, J Mellors2, and J Coffin1 1HIV Drug Resistance Prgm., NCI, NIH, DHHS, Frederick, MD, USA; 2Univ. of Pittsburgh, PA, USA; and 3Lab. of Immunoregulation, NIAID, NIH, DHHS, Bethesda, MD, USA BACKGROUND: Understanding the emergence and decay of drug-resistant HIV-1 variants is important for designing optimal antiretroviral treatment strategies. Standard genotyping methods do not reliably detect minor variants comprising less than 25% of the virus population and are not quantitative. We have therefore develo |
| 38 | HIV Resistance and Transmission following Single-dose Nevirapine in a PMTCT Cohort Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 38) N Martinson*1,2,3, L Morris1,2,3, G Gray1,2, D Moodley4, P Lupondwana1,2, C Chezzi1,2, S Cohen1, C Pillay1,2, A Puren1, M Ntsala1, J Sullivan5, J Steyn2, and J McIntyre2 1Natl. Inst. for Communicable Diseases, Johannesburg, South Africa; 2Perinatal HIV Res. Unit, Johannesburg, South Africa; 3Sch. of Med., Johns Hopkins Univ., Baltimore, MD, USA; 4King Edward Hosp., Durban, South Africa; and 5Univ. of Massachusetts Med. Sch., Worcester, USA BACKGROUND: Nevirapine (NVP), given to mothers in labor and to neonates within 72 hours of delivery, is an effective, simple PMTCT regimen. Previous studies have shown that transient resistance develops in those exposed to this regimen. This study was designed to assess genotypic resistance induced by NVP (NVPR). |
| 39 | Low-frequency NNRTI-resistant Variants Contribute to Failure of Efavirenz-containing Regimens Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 39) J Mellors*1, S Palmer2, D Nissley2, M Kearney2, E Halvas1, C Bixby1, L Demeter3, S Eshleman4, K Bennett5, S Hart6, F Vaida5, M Wantman5, J Coffin2, and S Hammer for the ACTG 398 Study Group7 1Univ. of Pittsburgh, PA, USA; 2Drug Resistance Prgm., NCI, NIH, DHHS, Frederick, MD, USA; 3Univ. of Rochester, NY, USA; 4Johns Hopkins Univ., Baltimore, MD, USA; 5Harvard Sch. of Publ. Hlth., Boston, MA, USA; 6Frontier Sci. and Technology Res. Fndn., Amherst, NY, USA; and 7Columbia Univ., New York, NY, USA BACKGROUND: The role of minor (low-frequency) drug-resistant variants in failure of antiretroviral therapy is not defined. In ACTG 398, 212 NNRTI-experienced and 269 NNRTI-naïve patients were randomized to efavirenz (EFV), abacavir , adefovir, and |
| 40LB | A Randomized, Double-blind Trial Assessing the Efficacy of Single-dose Perinatal Nevirapine Added to a Standard Zidovudine Regimen for the Prevention of Mother-to-child Transmission of HIV-1 In Thailand Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 40LB) M Lallemant*1, G Jourdain2, S Le Coeur3, J Y Mary4, N Ngo-Giang-Huong2, S Koetsawang5, S Kanshana6, K McIntosh7,8, V Thaineua6, and the Perinatal HIV Prevention Trial (Thailand) 1PHPT- Inst. de Recherche pour le Développement, France and Thailand; 2Harvard Sch. of Publ. Hlth., Boston, MA, USA; 3Inst. Natl. d’Etudes Démographiques, Paris, France; 4INSERM Erm 0321, Paris, France; 5Family Hlth. Res. Ctr., Mahidol Univ., Bangkok, Thailand; 6Ministry of Publ. Hlth., Bangkok, Thailand; 7Children’s Hosp., Boston, MA, USA; and 8Harvard Med. Sch., Boston, MA, USA BACKGROUND: Although zidovudine prophylaxis initiated at 28 weeks decreases in utero transmission of HIV to 1 to 2%, significant peripartum transmission still occurs. We hypothesized that, without additional toxicity, logistical complications, or significant cost, perinatal NVP added to ZDV could further reduce intrapa |
| 41LB | Exposure to Intrapartum Single-dose Nevirapine and Subsequent Maternal 6-Month Response to NNRTI-based Regimens Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 41LB) G Jourdain*1, N Ngo-Giang-Huong1, P Tungyai2, A Kummee2, C Bowonwatanuwong3, P Kantipong3, P Lechanachai4, S Hammer5, M Lallemant2, and Perinatal HIV Prevention Trial Group 1Harvard Sch. of Publ. Hlth., Boston, MA, USA; 2PHPT-Inst. de Recherche pour le Développement, France and Thailand; 3Ministry of Publ. Hlth., Bangkok, Thailand; 4Chiang Mai Univ., Faculty of Associated Med. Sci., Thailand; and 5Columbia Univ. Med. Ctr., New York, NY, USA BACKGROUND: Single-dose nevirapine (SD-NVP) is efficacious in preventing HIV mother-to-child transmission (PMTCT) but resistance mutations to non-nucleoside reverse transcriptase inhibitors (NNRTI) are detectable in the postpartum period in a substantial proportion of mothers. Their clinical significance is unknown. |
| 42 | Peripheral Neuropathy Associated with HIV and ARV: Update on Diagnosis and Management Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11: (abstract No. 42) Abrams E; Harlem Hosp Ctr, Columbia Univ, New York, NY, USA Enormous strides in care and treatment have led to dramatic reductions in mother-to-child- transmission (MTCT) in high resource settings. Widespread use of potent combination therapies during pregnancy coupled with intrapartum and postpartum treatment to the newborn has resulted in MTCT rates of 1-2%.Similarly, the eff |
| 43 | HIV Capture and Transmission by Dendritic Cells Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11: (abstract No. 43) Cunningham AL, Turville SG, Wilkinson J, Santos J, Frank I, Cameron P, Dable J, Hart D, Romani N, Lifson JD, Pope M; Ctr for Virus Res, Westmead, Australia BACKGROUND: Dendritic cells play a major role in HIV pathogenesis. Epithelial dendritic cells appear to be one of the first cells infected after sexual transmission and transfer of the virus to CD4 lymphocytes, simultaneously activating these cells to produce high levels of HIV replication. Such transfer may occur loca |
| 44 | Enhancement of HIV Infection by Activated Dendritic Cells Occurs via Trafficking through a CD81 Enriched Compartment Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11: (abstract No. 44) McDonald D, Hope TJ; Univ of Illinois, Chicago, USA BACKGROUND: Monocyte-derived dendritic cells (DC) efficiently bind and internalize HIV but are not easily infected by the virus despite adequate expression of entry receptors. Instead, DC can transmit infectious HIV to target cells, effectively completing an intracellular phase of the virus life cycle in the absence of |
| 45 | HIV-1 Spread between T Cells via a Virological Synapse Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11: (abstract No. 45) Sattentau QJ, Jolly C; The Sir William Dunn Sch of Pathology, Univ of Oxford, UK BACKGROUND: HIV-1 can spread both by release of cell-free virions and by direct cell-cell spread. Cell-cell spread has advantages for the virus including production of new viral RNA and proteins that is more rapid than that observed after cell-free virus infection, and potential escape from elements of humoral immunity |
| 46 | HIV Assembly in, and Release from, Primary Macrophages Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11: (abstract No. 46) Marsh M, Pelchen-Matthews A, Kramer B, Byland R, Deneka M, Fraile-Ramos A; Univ Coll, London, UK BACKGROUND: HIV types 1 and 2, and SIV, are generally thought to assemble at the plasma membrane of infected cells. METHODS: We investigated virus assembly by immunolabeling cryosections of HIV-1-infected primary human monocyte-derived macrophages (MDM). Using fluorescence and electron microscopy we found virus particl |
| 47 | Disorders of Bone Mass and Bone Metabolism Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11: (abstract No. 47) Mora S, Zamproni I, Sciannamblo M, Giacomet V, Vigano A; Sci Inst H S Raffaele, Milan, Italy BACKGROUND: The development of precise non-invasive methods for measuring bone mineral content has significantly improved our ability to study the changes in bone mass occurring during growth. The most commonly employed method for the assessment of bone mineral content is dual-energy x-ray absorptiometry (DXA). Bone mi |
| 48 | Mitochondrial Toxicity Resulting from the Treatment of Pregnant Women and Infants Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11: (abstract No. 48) Blanche S;;; Hosp Necker, Paris, France BACKGROUND: Mitochondrial toxicity of some nucleoside analogues, when used alone or in association, is now well established. These molecules can cross the placenta, such that the foetus is often exposed for several months. There is no reason to believe that the fetus or the infant is not subject to this phenomenon. Ult |
| 49 | Psychiatric Co-morbidity in HIV Infected Youth Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11: (abstract No. 49) Nachman S;;; Stony Brook Univ, NY, USA BACKGROUND: As the HIV epidemic enters its third decade, advances in treatment have transformed the disease from a rapidly fatal infection to a chronic illness. Newer complications, such as psychiatric comorbidity, possibly related to both HIV and its treatments, are emerging. Psychological manifestations in children w |
| 50 | Dyslipidemia, Osteopenia and Changes in Body Habitus in HIV-Infected Women Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11: (abstract No. 50) Schoenbaum EE;;; Montefiore Med Ctr, Albert Einstein Sch of Med, Bronx, NY, USA BACKGROUND: Since the advent of HAART, dyslipidemia, osteopenia, and changes in body habitus have been observed in HIV-infected women and men. Studies have linked these findings to anti-retroviral medications, HIV itself, and classic risk factors seen in an aging population. For women with HIV, menopause increases the |
| 51 | Poor Virologic Responses and Early Emergence of Resistance in Treatment Naïve, HIV-infected Patients Receiving a Once Daily Triple Nucleoside Regimen of Didanosine, Lamivudine, and Tenofovir DF Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 51) J Jemsek*, P Hutcherson, and E Harper; Jemsek Clin., Huntersville, NC, USA BACKGROUND: The role of triple nucleoside analog reverse transcriptase inhibitor (NRTI) regimens remains uncertain for patients at various stages of HIV infection. We recently undertook a 24-week pilot study to evaluate the potency and safety of a once-daily regimen of didanosine EC ( |
| 52 | Low Genetic Barrier to Resistance Is a Possible Cause of Early Virologic Failures in Once-Daily Regimen of Abacavir, Lamivudine, and Tenofovir: The Tonus Study Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 52) R Landman*1, G Peytavin1, D Descamps1, F Brun Vezinet1, H Benech1,8, A Benalisherif1,2, A Trylesinski2,3, C Katlama3,4, P M Girard4,5, F Raffi1, P Yeni6, M Bentata6, B Jarrousse6,7, C Michelet7,8, P Flandre9, Tonus Study Group, and Tonus study group; 1Bichat Claude Bernard Hosp., Paris, France; 2Gilead Sci., Paris, France; 3Pitié-Salpêtrière Hosp., Paris, France; 4Saint Antoine Hosp., Paris, France; 5CHU Nantes, Hosp. Nantes, France; 6Avicennes Hosp., Bobigny, France; 7CHU Rennes, France; 8CEA Lab., Orsay, France; and 9Inserm U472. Villejuif, France BACKGROUND: High rates of early virological failure have been reported in naïve patients who received the triple nucleoside/nucleotide once daily regimen of abacavir (ABC), lamivudine ( 3TC |
| 53 | COL40263: Resistance and Efficacy of Once-daily Trizivir and Tenofovir DF in Antiretroviral Naïve Subjects Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 53) R Elion*1, C Cohen2, E DeJesus3, R Redfield4, J Gathe5, R Hsu6, L Yau7, L Ross7, B Ha7, R Lanier7, T Scott7, and COL40263 study team 1George Washington Sch. of Med., Washington DC, USA; 2Community Res. Initiative of New England, Boston, MA, USA; 3IDC Res. Initiative, Altamonte Springs, FL, USA; 4Inst. of Human Virology, Baltimore, MD, USA; 5Therapeutic Concepts, P.A., Houston, TX, USA; 6St. Vincent's Hosp., New York, NY, USA; and 7GlaxoSmithKline, Research Triangle Park, NC, USA BACKGROUND: This is a pilot, open-label, multicenter study evaluating the efficacy and safety of once-daily trizivir (TZV) + Tenofovir DF (TDF) in antiretroviral naïve subjects with entry HIV-1 RNA >30,000 copies/mL. |
| 54 | K65R: A Multinucleoside Resistance Mutation of Increasing Prevalence Exhibits Bi-directional Phenotypic Antagonism with TAM Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 54) U Parikh*1, D Koontz1, N Sluis-Cremer1, J Hammond2, L Bacheler3, R Schinazi4, and J Mellors1 1Univ. of Pittsburgh, PA, USA; 2Agouron Pharm., La Jolla, CA, USA; 3VircoLab Inc., Durham, NC, USA; and 4Emory Univ., Atlanta, GA, USA BACKGROUND: The 65R mutation in HIV-1 RT is selected in vitro by many D-nucleosides but has been paradoxically rare in vivo until recently. In the GS903 and ES30009 trials, 65R emerged in 24 to 54% of patients experiencing virologic failure on regimens containing tenofovir (without |
| 55 | The HIV-1 K65R RT Mutant Utilizes a Combination of Decreased Incorporation and Decreased Excision to Evade NRTI Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 55) K L White*1, N A Margot1, J M Chen1, R Wang1, M Pavelko1, T Wrin2, C J Petropoulos2, M McDermott1, S Swaminathan1, and M D Miller1 1Gilead Sci., Inc., Foster City, CA, USA and 2ViroLogic Inc., South San Francisco, CA, USA BACKGROUND: The HIV-1 reverse transcriptase (RT) mutation K65R is selected by the nucleoside and nucleotide RT inhibitors (NRTI) ddI , abacavir, tenofovir , and d4T . |
| 56 | Randomized, Placebo-Controlled Trial of Abacavir Intensification in HIV-1-infected Adults with Plasma HIV RNA <500 Copies/mL Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 56) S Hammer*1, R Bassett2, M Fischl3, K Squires4, L Demeter5, J Currier6, G Morse7, V DeGruttola2, C Lalama2, S Snyder8, J Mellors9, ACTG 372A Study Team10, and Adult AIDS Clinical Trials Group 1Columbia Univ., New York, NY, USA; 2Harvard Sch. of Publ. Hlth., Boston, MA, USA; 3Univ. of Miami, FL, USA; 4Univ. of Southern California, Los Angeles, USA; 5Univ. of Rochester, NY, USA; 6Univ. of California, Los Angeles, USA; 7State Univ. of New York, Buffalo, NY; 8AACTG Operations Ctr., Rockville, MD, USA; 9Univ. of Pittsburgh, PA, USA; and 10NIAID-sponsored AACTG, Bethesda, MD, USA BACKGROUND: Maximizing durability of viral suppression is an important goal of antiretroviral therapy. The objective of ACTG 372A was to determine if the intensification strategy of adding abacavir (ABC) to an effective indinavir (IDV)-dual NRTI regimen would delay |
| 57 | Detection of Pre-existing Minority Viral Populations Contributing to the Evolution of Resistance to Protease Inhibitors. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 57) Charpentier C, Morand-Joubert L, Chene G, Girard PM, Clavel F, Hance AJ; INSERM U552, Paris, France BACKGROUND: In patients harboring PI-resistant HIV-1, the virologic response to treatment changes introducing new PI is often transient, due to the emergence of variants with additional protease mutations and extended cross-resistance. We have investigated the role of preexisting minority virus populations in this evol |
| 58 | A 16-week Treatment Interruption Does Not Improve the Virologic Response to Multidrug Salvage Therapy in Treatment-experienced Patients: 48-week Results from ACTG A5086 Conf Retrovir Opportunistic Infect 2004 Febr 8 11;11: (abstract No. 58) Benson C, Downey G, Havlir DV, Vaida F, Lederman M, Gulick R, Glesby M, Patel S, Wantman M, Bixby C, Pettinelli C, Rinehart A, Snyder S, Mellors J, and the ACTG A5086 Study Team; Univ. of Colorado Hlth. Sci. Ctr., Denver, USA BACKGROUND: Data are conflicting on the clinical and virologic response to antiretroviral therapy (ART) following structured treatment interruption (STI) in patients with multidrug resistant HIV-1. METHODS: A5086 was a phase 3, open-label, prospective, randomized, multicenter trial evaluating the efficacy of STI in hea |
| 59 | HIV-1 Subtype-related Differences in Genotypic Evolution: Analysis of Subtypes B and C Reverse Transcriptase and Protease Sequences. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 59) Kantor R, Shafer RW, Efron B, Camacho R, Harrigan PR, Tanuri A, Pillay D, Weber J, Vandamme AM, Phanuphak P, Sugiura W, Soriano V, Morris L, Schapiro JM, Katzenstein D; Stanford Univ., CA, USA BACKGROUND: Subtype C is the most prevalent HIV-1 subtype worldwide. With increased treatment access, differences between B and C in the reverse transcriptase (RT) and protease genes may influence virus susceptibility, selection of mutations and genotypic interpretation of resistance. The impact of subtype on the evolu |
| 60 | HLA Imprinting: Implications for Selection of Vaccine Immunogens. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 60) Mallal S; Ctr for Clin Immunology and Biomed Statistics, Royal Perth Hosp, Australia BACKGROUND: Human leukocyte antigens (HLA) are the most polymorphic human proteins, with over 1300 distinct alleles defined to date. At the individual level, the inheritance of specific HLA alleles shape the immune response in a manner that is analogous to antiretroviral drugs, in that each allele provides a specific s |
| 61 | DNA Editing and Host Resistance Factors. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 61) Neuberger M; Med Res Council, Cambridge, UK BACKGROUND: Many pathways in living organisms are devoted to repairing any modifications that occur to the bases in DNA or changes to its sequence since such changes usually lead to mutations that are deleterious and can predispose to cancer. Recent work, however, has revealed physiological programs of directed attack |
| 62 | HIV-1 Vif Overcomes the Innate Antiviral Activity of APOBEC3G by Promoting its Degradation in the Ubiquitin-Proteasome Pathway. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 62) Mehle A, Strack B, Ancuta P, Gabuzda D; Dana-Farber Cancer Inst., Boston, MA, USA and 2Harvard Med. Sch., Boston, MA, USA BACKGROUND: The HIV Vif protein is essential for production of infectious virus. Vif counteracts the innate antiviral activity of APOBEC3G, a cytidine deaminase that induces massive G to A hypermutation in the viral genome. In the absence of Vif, APOBEC3G incorporation into virions renders HIV non-infectious. Here, we |
| 63 | Characterization of Mutations Generated by APOBEC3G on HIV-1 DNA. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 63) Yu Q, Konig R, Pillai S, Kearney M, Palmer S, Richman D, Coffin J, Landau NR; Salk Inst. for Biological Studies, La Jolla, CA, USA BACKGROUND: HIV-1 vif blocks the antiviral activity of human APOBEC3G, a cellular cytosine deaminase. APOBEC3G encapsidated into the vif-deleted virions deaminates cytosines of the viral reverse transcripts to uracil on the next round of infection. HIV-1 vif does not block the antiviral activity of primate and mouse AP |
| 64 | AIP1 and ESCRT-III Are Components of the HIV-1 Budding Machinery. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 64) Strack B, Calistri A, Popova E, Craig S, Gottlinger H; Dana-Farber Cancer Inst., Boston, MA, USA BACKGROUND: HIV-1 budding requires a membrane fission event to release the nascent virion. This membrane fission event is promoted by the p6 domain of Gag, which recruits Tsg101, a component of the class E vacuolar protein sorting (Vps) machinery. We find that HIV-1 p6 contains a second region involved in budding that |
| 65 | Cell-type-specific Targeting of HIV-1 Gag: Evidence of a Role for PIP2. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 65) Ono A, Freed EO; NCI-FCRDC, NIH, DHHS, Frederick, MD, USA BACKGROUND: HIV-1 particle formation begins with the targeting of the viral structural protein Gag to the site of virus assembly. In most cell types, including HeLa and T cells, virus assembly takes place largely on the plasma membrane, whereas in macrophages virus particles are mainly formed in intracellular vesicles. |
| 66 | Visualization of HIV-1 P55-GFP In Living Cells. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 66) Gomez CY, Hope TJ; Univ. of Illinois at Chicago, USA BACKGROUND: Studies have shown that several cellular factors play key roles in the assembly and budding processes in HIV. In addition, the assembly of viral proteins varies among different cell types. We have shown that the HIV matrix protein accumulates in actin-dependent structures and we hypothesize that this may re |
| 67 | Capsid Determines the Infectivity of Retroviruses in Nondividing Cells by Mediating Nuclear Transport of Incoming Virions. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 67) Yamashita M, Emerman M; Fred Hutchinson Cancer Res. Ctr., Seattle, WA, USA BACKGROUND: A major difference between lentiviruses such as HIV and most other retroviruses (such as the murine leukemia virus, MLV) is their ability to productively infect nondividing cells. Previous studies demonstrated that it is possible to make infectious chimeric viruses in which MA of MLV was replaced by HIV MA |
| 68 | Characterization of the Role of LEDGF during HIV Replication. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 68) Debyser Z, Emiliani S, Maele BV, Vercammen J, Maroun M, Busschots K, Cherepanov P, De Clercq E, Rain JC, Benarous R; The European TRIoH Consortium, Rega Inst. for Med. Res., Katholieke Univ. Leuven, Belgium BACKGROUND: LEDGF (lens epithelium-derived growth factor, p75) interacts tightly with HIV-1 integrase and is essential for nuclear targeting of this protein in human cells. A large-scale yeast 2-hybrid screen independently revealed LEDGF as a binding partner of HIV-1 integrase. METHODS: We have now mapped the molecular |
| 69 | HIV-1 Nef Mediates Vascular Endothelial Cell Signals Greatly Enhancing HIV-1 Replication in Extra-nodal CD4+ Memory T cells. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 69) Walker J, Choi J, Boichuk S, Kirkiles-Smith N, Pober JS, Alexander L; Yale Univ., New Haven, CT, USA BACKGROUND: Late in the course of infection, in the absence of intact lymphoid tissue, HIV-1 replicates efficiently in extra-nodal, peripheral tissues. We hypothesized that in this microenvironment, as in lymph node, local factors can enhance viral replication. METHODS and RESULTS: We have discovered that a likely cons |
| 70 | Replication-competent Variants of HIV-2 with Deletions of the V3 Hypervariable Loop. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 70) Bertolotti-Ciarlet A, Lin G, Biscone M, Haggarty B, Romano J, Doms RW, Hoxie JA; Univ. of Pennsylvania, Philadelphia, USA BACKGROUND: Hypervariable loops V1/V2 and V3 on the HIV gp120 envelope protein (Env) facilitate interactions with chemokine receptors and contain neutralizing epitopes. They also may protect conserved domains on the gp120 core from humoral immune responses. The V3 loop determines tropism and participates directly in ch |
| 71 | Mimicking an Integrin Receptor Signal, HIV-1 Nef Recruits the PcG Protein Eed to Activate HIV Transcription. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 71) Witte V, Laffert B, Blume K, Sixt M, Rosorius O, Lischka P, Baur AS; Univ. of Erlangen, Germany and 2Inst. of Clin. and Molecular Virology, Univ. of Erlangen, Germany BACKGROUND: It has been shown that Nef increases the viral load in the infected host by enhancing viral infectivity and particle release. Whether Nef-mediated signalling in T cells directly targets viral transcription is not clear. METHODS: A yeast 2-hybrid system was used to screen for a novel Nef-interacting protein. |
| 72 | Population Prevalence of Hepatic Steatosis among Antiretroviral-experienced HCV/HIV Co-infected Adults with and without Stavudine Exposure. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 72) Sulkowski M, Mehta S, Moore R, Torbenson M, Chaisson R, Astemborski J, Thomas D; Johns Hopkins Univ., Baltimore, MD, USA BACKGROUND: Hepatic steatosis has been associated with antiretroviral therapy (ART) and, among those with HCV, with increased fibrosis progression and decreased response to HCV therapy. The study objective was to determine the prevalence and correlates of steatosis in HCV/HIV co-infected patients. METHODS: We randomly |
| 73 | Prevalence and Incidence of Pre-diabetes and Diabetes in the Multicenter AIDS Cohort Study Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 73) T T Brown*1, S R Cole1, X Li1, L A Kingsley2, F J Palella Jr3, S A Riddler2, B R Visscher4, J B Margolick1, and A S Dobs1; 1Johns Hopkins Univ., Baltimore, MD, USA; 2Univ. of Pittsburgh, PA, USA; 3Northwestern Univ., Chicago, IL, USA; and 4Univ. of California, Los Angeles, USA BACKGROUND: Abnormalities in glucose metabolism have been described with increasing frequency in patients with HIV and may result from both direct and indirect effects of highly active antiretroviral therapies (HAART). The incidence and prevalence of pre-diabetes and diabetes (DM) and their relationship to antiretrovir |
| 74 | Prospective Study of Glucose and Lipid Metabolism in Antiretroviral-Naïve Subjects Randomized to Receive Nelfinavir, Efavirenz, or Both Combined with Zidovudine+Lamivudine (ZDV+3TC) or Didanosine+Stavudine: A5005s, a Substudy of ACTG 384 Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 74) M Dubé*1, R Zackin2,3, R Parker2,3, Y Yang2,3, S Grinspoon3, P Tebas4, G Robbins3, R Shafer5, S Snyder6, K Mulligan7, and Adult AIDS Clinical Trials Group 1Indiana Univ, Indianapolis, IN, USA; 2Statistical and Data Analysis Ctr., Boston, MA, USA; 3Harvard Univ., Boston, MA, USA; 4Washington Univ., St. Louis, MO, USA; 5Stanford Univ., Palo Alto, CA, USA; 6ACTG Operations Ctr., Silver Spring, MD, USA; and 7Univ. of California, San Francisco, USA BACKGROUND: The primary objective of A5005s was to determine whether nelfinavir (NFV)- and efavirenz (EFV)-based therapies differ with respect to changes in fasting lipids and insulin resistance. Secondary objectives included comparisons among NRTI regimens. |
| 75 | Predictors of Hypertension and Changes in Blood Pressure in HIV-infected Patients in the D:A:D Study Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 75) R Thiébaut*1, W El-Sadr2, G Chenuc1, N Friis-Moller3, M Rickenbach4, P Reiss5, A D’Arminio Monforte6, L Morfeldt7, C Pradier8, O Kirk9, S De Wit10, G Calvo11, M Law12, C Sabin13,14, J D Lundgren3, and D:A:D Study group; 1Aquitaine Cohort, C.H.U. Bordeaux, INSERM U593, Bordeaux, France; 2CPCRA, Columbia Univ./Harlem Hosp., New York, NY, USA; 3Copenhagen HIV Prgm., Hvidovre Univ. Hosp., Denmark; 4SHCS, Ctr. Hosp. Univ. Vaudois, Lausanne, Switzerland; 5ATHENA, HIV Monitoring Fndn., Academic Med. Ctr., Amsterdam, The Netherlands; 6ICONA, L Sacco Hosp., Univ. of Milan, Milan, Italy; 7HivBivus, Karolinska Hosp., Stockholm, Sweden; 8Nice Cohort, CHU Nice Hosp. de l'Archet, France; 9EuroSIDA, CHIP, Hvidovre Univ. Hosp., Copenhagen, Denmark; 10Saint-Pierre Cohort, CHU Saint-Pierre Hosp., Brussels, Belgium; 11BASS, Autonomous Univ. of Barcelona, Spain; 12AHOD, Natl. Ctr. in HIV Epidemiology and Clin. Res., Sydney, Australia; 13Royal Free Ctr. for HIV Med., Royal Free and Univ. Coll., London, UK; and 14Univ. Coll. London, UK BACKGROUND: Hypertension is a well-known cardiovascular risk factor. Factors affecting the blood pressure of HIV-infected patients are poorly understood, although it has been hypothesised that anti-HIV drugs may lead to elevations. We assessed predictors of changes in systolic and diastolic blood pressure and of occurr |
| 76 | Nucleoside Reverse Transcriptase Inhibitors Decrease Mitochondrial and PPARgamma Gene Expression in Adipose Tissue after only 2 Weeks in HIV-uninfected Healthy Adults. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 76) P Mallon*1,2, P Unemori1, M Bowen2, J Miller3, M Winterbotham1, A Kelleher1,2, K Williams2, D Cooper1,2, and A Carr2 1Natl. Ctr. in HIV Epidemiology and Clin. Res., Univ. of New South Wales, Sydney, Australia; 2St. Vincent’s Hosp., Sydney, Australia; and 3Garvan Inst. of Med. Res., Sydney, Australia Background: Long-term NRTI therapy often leads to lipoatrophy. Although NRTI may inhibit adipocyte DNA polymerase-g, affecting mitochondrial (mt) replication and oxidative phosphorylation, published data are contradictory and it is unclear whether mtDNA depletion is the primary defect in NRTI-induced toxicity. Methods: |
| 77 | Effects of Pravastatin on Lipoproteins and Endothelial Function in Patients Receiving HIV Protease Inhibitors Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 77) J Sosman*, M Merwood, J Bellehumeur, S Aeschlimann, C Korcarz, G Underbakke, M Mays, and J Stein Univ. of Wisconsin Med. Sch., Madison, USA BACKGROUND: The use of PI in HIV has been associated with dyslipidemia and vascular endothelial dysfunction, which may predispose patients to atherosclerosis. Although pravastatin is recommended as initial therapy for dyslipidemic patients taking PI, pravastatin s effects on lipoproteins and vascular endothelial functi |
| 78 | Metabolic Changes in Patients Switching from a Protease Inhibitor-Containing Regimen to Abacavir, Efavirenz,) or Nevirapine: 24-Month Results of a Randomized Study. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 78) Fisac C, Fumero E, Crespo M, Roson B, Virgili N, Ribera E, Ferrer E, Gatell JM, Podzamczer D; Hosp. Univ. de Bellvitge, L'Hospitalet, Barcelona, Spain BACKGROUND: Switching to a PI-sparing regimen is a common therapeutic strategy for patients with metabolic and lipodystrophic changes. METHODS: NEFA was an open-label randomized study comparing 3 different PI-sparing regimens (ABC, EFV, and NVP) in HIV+ individuals who had been previously exposed to a HAART PI-containi |
| 79 | Rosiglitazone for the Treatment of HIV Lipoatrophy: A Double-blind, Placebo-controlled, 48-week Trial Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 79) A Carr*1, C Workman2, G Rogers3, A Martin4, D Carey4, D Baker5, H Wand4, M Law4, K Samaras1,6, S Emery4, D Cooper4, and ROSEY study group 1St. Vincent's Hosp., Sydney, Australia; 2AIDS Res. Initiative, Sydney, Australia; 3Care and Prevention Gen. Practice, Adelaide, Australia; 4Natl. Ctr. in HIV Epidemiology and Clin. Res., Univ. of New South Wales, Sydney, Australia; 5407 Doctors, Sydney, Australia; and 6Garvan Inst. of Med. Res., Sydney, Australia BACKGROUND: There is no clinically effective therapy for HIV lipodystrophy except switching from thymidine nucleoside analogue (NRTI) therapy. Thiazolidinediones such as rosiglitazone (RSG) promote subcutaneous fat growth, decrease visceral fat, and improve glycemic and lipid parameters in type 2 diabetics and in adult |
| 80 | Low-dose Maintenance Therapy with Recombinant Human Growth Hormone Sustains Effects of Previous r-hGH Treatment in HIV+ Patients with Excess Center Fat: Treatment Results at 60 Weeks Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 80) D P Kotler*1, C Grunfeld2, N Muurahainen3, C Wanke4, M Thompson5, D Bock3, J Gertner3, and Serostim in the Treatment of Adipose Redistribution Syndrome (STARS) Trial Investigator Group 1Columbia Univ. and St. Lukes Hosp. Ctr., New York, NY, USA; 2Univ. of California, San Francisco, VA Med. Ctr., USA; 3Serono, Inc., Rockland, MA, USA; 4Tufts Univ. Sch. of Med., Boston, MA, USA; and 5AIDS Res. Consortium of Atlanta, GA, USA BACKGROUND: This prospective, multi-center, randomized, dose-finding extension trial evaluated the efficacy and safety of r-hGH ( Serostim ) maintenance therapy, 1 or 2 mg daily, to sustain reductions of trunk fat and cholesterol concentrations induced by prior treatment with higher-dose r-hGH. In the antecedent STARS |
| 81 | Incidence of Non-AIDS-defining Malignancies in the HIV Outpatient Study Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 81) P Patel*1, R M Novak2, T Tong1, P Behari2, A Moorman1, F J Palella Jr2, S D Holmberg1, and HIV Outpatient Study (HOPS) 1Atlanta, GA, USA and 2Chicago, IL, USA BACKGROUND: Studies have shown a decline in AIDS-defining malignancies since the advent of highly active antiretroviral therapy (HAART). However, the incidence of non-AIDS defining cancers among HIV-infected individuals seem to be increasing. We determined the incidence of 5 cancers among HIV Outpatient Study (HOPS) pa |
| 82 | Surgical Outcomes of HIV+ Patients in the Era of HAART. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 82) Horberg M, Hurley L, Klein D, Follansbee S, Flamm J, Green G; Kaiser-Santa Clara, CA, USA BACKGROUND: The perception remains that HIV+ patients would have a worse surgical outcome than HIV- patients because of suppressed immune status and poor viral control. In a matched design we compared HIV+ patients to HIV- patients with respect to surgical outcomes in the HAART era. METHODS: All selected procedures (ap |
| 83 | Men on the 'Down Low': More Questions than Answers. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 83) Millett G; CDC, Atlanta, GA, USA BACKGROUND: Men on the down low, a subgroup of bisexually active black men has become a focal point of interest in the HIV prevention community in the past several years. One of the primary reasons for this is the question of whether men on the down low function as an HIV transmission bridge to the heterosexual populat |
| 84 | Transmission on Campus: Insights from Tracking HIV Incidence in North Carolina Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 84) L B Hightow*1, P MacDonald1, C D Pilcher1, A H Kaplan1, E Foust2, T Q Nguyen1, and P A Leone1 1Univ. of North Carolina at Chapel Hill, USA and 2North Carolina Dept. of Hlth. and Human Svcs., Raleigh, USA BACKGROUND: Surveillance for HIV has been limited to monitoring HIV seroprevalence populations. This method has limited ability to detect increasing incidence or clustering within specific risk groups or geographic areas. Beginning in November 2002, North Carolina’s Screening and Tracing Active Transmission (STAT) Prog |
| 85LB | Investigation of HIV Transmission in Black MSM College Students and Non-Students in North Carolina. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 85LB) Fitzpatrick L, Grant L, Eure C, Phillip S, Millett G, Jones K, Hightow L, Stall R, Leone P, Holmberg S, Foust E, Greenberg A; CDC, Atlanta, GA BACKGROUND: In May 2003, the North Carolina Department of Health identified 49 new cases of HIV among black men who have sex with men (MSM) (all college students) and consequently, in August 2003 invited CDC to assist with an in-depth epidemiologic and behavioral investigation. METHODS: A survey was conducted to assess |
| 86 | Recent Trends in HIV Diagnoses in the United States. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 86) Hall HI, Ling Q, Song R, McKenna MT; CDC, Atlanta, GA, USA BACKGROUND: Recent outbreaks of syphilis among men who have sex with men and increasing prevalence of unprotected sex have raised concerns of potential increases in HIV transmission. METHODS: Using data from 29 states with confidential reporting of HIV/AIDS cases diagnosed during 1999 through 2002, we determined annual |
| 87 | Descriptive Epidemiology of HIV/AIDS in New York City: Incorporation of Newly Available Population-based Surveillance Data on HIV (non-AIDS), 2001. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 87) Nash D, Manning SE, Ramaswamy C; New York City Dept. of Hlth. and Mental Hygiene, HIV Surveillance and Epidemiology Prgm., NY, USA and 2CDC, Epidemic Intelligence Svc., State Branch, Atlanta, GA, USA BACKGROUND: Prior to the implementation of regulations in June 2000 requiring New York health care providers and laboratories to report newly diagnosed HIV infection (non-AIDS), the HIV epidemic in New York City was monitored primarily through AIDS-case reporting. We report on the descriptive epidemiology of HIV/AIDS i |
| 88 | Trends in Primary and Secondary Syphilis and HIV Seroincidence among Men Who Have Sex with Men in San Francisco, 1998-2002. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 88) Buchacz K, Kellogg T, McFarland W, Kohn R, Dilley J, Louie B, Kent C, Holmberg S, Klausner J; CDC, Atlanta, GA, USA BACKGROUND: Syphilis facilitates the acquisition and transmission of HIV infection. To explore whether the current syphilis epidemic has been associated with increases in HIV incidence in San Francisco, we examined trends in HIV incidence in men who have sex with men (MSM) in 2 HIV testing populations and rates of prim |
| 89 | A 15-year Retrospective in Trends in Incidence, Prevalence and Risk Factors for HIV Infection among Inner City Patients Attending the Johns Hopkins Emergency Department, 1988 to 2003. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 89) Henson C, Laeyendecker O, Kraus C, Horne BJ, Rothman RE, Shahan JB, Kelen GD, Quinn TC; Johns Hopkins Univ., Balitmore, MD, USA and 2NIAID, NIH, DHHS, Bethesda, MD, USA BACKGROUND: We wanted to determine the temporal trends in HIV prevalence, incidence, and associated risk behaviors in adults attending the Johns Hopkins Hospital Emergency Department (JHH ED) from 1988 to 2003. METHODS: Identity-unlinked sero-survey studies were performed in 1988, 1992, 2000, 2001, and 2003 at the JHH |
| 90 | The Effect of Various Counseling and Testing Methods on the Rate of HIV Testing among Male Prisoners. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 90) Baham J, Gavin J, Mittal S, Kuniholm M, Harriss D, Ruiz J, Bick J; California Dept. of Hlth. Svcs., Office of AIDS, Richmond, USA BACKGROUND: HIV infection is more prevalent among inmates than in the non-incarcerated. About 25% of those with HIV in the United States will be incarcerated each year, and most are unaware of their serostatus. Early diagnosis can prevent the spread of HIV and reduce the incidence of AIDS. This study evaluated the effe |
| 91 | HIV/AIDS in Jails and Prisons. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 91) McAuley J; Cook County Jail, Chicago, IL, USA BACKGROUND: The adult justice system in the United States consists of police holding-cells, pre-trial detention centers (jails), and prisons (state, federal, military). The length of stay for jails varies by jurisdiction but is typically several days to a few weeks while prisons house persons for at least one year. The |
| 92 | Partially Reverse Transcribed HIV Genome in Uninfected HIV-exposed Infants. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 92) Lee FK, Scinicariello F, Ou CY, Bulterys M, Nesheim S; Emory Univ. Sch. of Med., Atlanta, GA, USA and 2CDC, Atlanta, GA, USA BACKGROUND: HIV-1 replication is influenced by the phase of cell cycle at the time of infection. It has previously been demonstrated that only partial reverse transcripts of HIV-1 DNA could be found in resting lymphocytes (G0-G1a). We postulate that a portion of perinatal HIV transmissions may involve initial entry of |
| 93 | Characterization of Breast Milk T Cells from HIV+ and HIV- Women Reveal Compartmentalization of Antigen Specific Responses. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 93) Edwards B, Ghosh M, Sabbaj S, Rhodes A, Decker D, Goepfert P, Aldrovandi G; Univ. of Alabama at Birmingham, USA and 2Childrens' Hosp. Los Angeles, CA, USA BACKGROUND: Transmission of HIV via breast milk is a significant source of pediatric infection, yet the majority of infants do not acquire infection through this route. This latter finding may be due to the low levels of HIV RNA in breast milk compared with plasma. We therefore hypothesized that the magnitude and quali |
| 94 | Consequences of Mother-Child Sharing of HLA Alleles for Clinical Disease Progression among Vertically Infected Children. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 94) Kuhn L, Abrams EJ, Palumbo P, Bulterys M, Aga R, Louie L, Hodge T; Columbia Univ., New York, NY, USA BACKGROUND: When children acquire HIV infection from their mother (with whom they share at least 50% of their HLA alleles), they acquire virus with a history of encounter with maternal HLA-mediated immune responses. We sought to investigate whether HLA selection pressure would adversely influence clinical outcomes of H |
| 95 | Performance of Rapid HIV-1 Testing at Labor and Delivery: A Multicenter Study. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 95) Bulterys M, Jamieson DJ, O'Sullivan MJ, Cohen MH, Maupin R, Nesheim S, Webber MP, Dyke RV, Wiener J, Branson BM; CDC, Atlanta, GA, USA BACKGROUND: Accurate and timely rapid HIV testing could allow HIV-infected women with undocumented HIV status, presenting at labor and delivery immediate access to antiretroviral prophylaxis. METHODS: The multicenter Mother-Infant Rapid Intervention at Delivery (MIRIAD) study implemented 24-hour counseling and voluntar |
| 96 | Combination Short-course Zidovudine plus 2-Dose Nevirapine for Prevention of Mother-to-Child Transmission: Safety, Tolerance, Transmission, and Resistance Results. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 96) Chalermchokcharoenkit A, Asavapiriyanont S, Teeraratkul A, Vanprapa N, Chotpitayasunondh T, Chaowanachan T, Mock P, Wilasrusme S, Skunodom N, Simonds RJ, Tappero JW, Culnane M; Siriraj Hosp., Bangkok, Thailand BACKGROUND: Both short-course zidovudine (ZDV) and a 2-dose regimen of oral intrapartum/newborn nevirapine (NVP) significantly reduce perinatal HIV-1 transmission. We studied the safety, tolerance, development of resistance, and transmission rates of combining these |
| 97 | Association between Antiretroviral Therapy during Pregnancy and Prematurity/Low Birth Weight Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 97) K Beckerman*1, D Covington2, P Garcia3, H Watts4, B Ross5, S Chavers6, S Sacks7, and H Tilson8 1New York Univ., NY, USA; 2PharmaRes. Corp., A Member of Inveresk Group, Wilmington, NC, USA; 3Northwestern Univ., Chicago, IL, USA; 4NICHD, NIH, DHHS, Rockville, MD, USA; 5Johns Hopkins Univ., Baltimore, MD, USA; 6GlaxoSmithKline, Research Triangle Park, NC, USA; 7F. Hoffman-La Roche Inc., Nutley, NJ, USA; and 8Univ. of North Carolina at Chapel Hill, USA BACKGROUND: Evidence is conflicting on the association between prematurity and the use of combination antiretroviral therapy (ART) during pregnancy. This study examines that association in a long-standing pregnancy exposure registry. METHODS: This study used data from the Antiretroviral Pregnancy Registry, an ongoing r |
| 98 | Pregnancy Outcome in ART-Treated HIV-Infected Women in Europe Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 98) C Thorne*, M Newell, and European Collaborative Study Inst. of Child Hlth., Univ. Coll. London, UK BACKGROUND: Although highly successful in reducing the risk of mother-to-child transmission, the increasing use of HAART in HIV-infected women in pregnancy may be associated with adverse pregnancy outcomes. METHODS: In the European Collaborative Study, HIV-infected pregnant women and their infants are followed up prosp |
| 99 | Mother-to-Child HIV Transmission Risk According to Antiretroviral Therapy, Mode of Delivery, and Viral Load in 2895 U.S. Women (PACTG 367) Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 99) D Shapiro*1, R Tuomala2,3, H Pollack4, S Burchett3,5, J Read6, M Cababasay1, J McNamara7, and G Ciupak8 1Harvard Sch. of Publ. Hlth., Boston, MA, USA; 2Brigham and Women's Hosp., Boston, MA, USA; 3Harvard Med. Sch., Boston, MA, USA; 4New York Univ. Sch. of Med., NY, USA; 5Children's Hosp.; 6NICHD, NIH, DHHS, Bethesda, MD, USA; 7NIAID, NIH, DHHS, Bethesda, MD, USA; and 8Frontier Sci. and Technology Res. Fndn., Buffalo, NY, USA BACKGROUND: Antiretroviral therapy (ART) during pregnancy and cesarean section before labor and membrane rupture (ECS) each reduce vertical HIV transmission, but their effects among women with low viral load are not well characterized. METHODS: Abstraction of medical records of HIV-infected pregnant women at 67 U.S. cl |
| 100 | Children but Not Adults Mount a Secondary Immune Response to a Variant HIV-1 Epitope following CTL Escape. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 100) Feeney M, Draenert R, Roosevelt K, Tang Y, Pfafferott K, Verrill C, Altfeld M, Walker BD, Goulder P; Massachusetts Gen. Hosp., Boston, MA BACKGROUND: Individuals expressing the HLA-B57 allele exhibit slow progression to AIDS and in the majority of such individuals the CTL response is dominated by B57-restricted epitopes. The p24 Gag epitope TSTLQEQIGW is the earliest epitope targeted during primary infection in B57+ subjects. We compared recognition of T |
| 101 | Defensive Arts: Antiviral Defense by APOBEC3G. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 101) Trono D; Univ of Geneva, Switzerland BACKGROUND: Viral replication most often requires that innate intracellular lines of defense be overcome. APOBEC-3G is a cytidine deaminase that exerts a broad antiretroviral activity by mediating the lethal editing of nascent reverse transcripts. It is countered by the Vif (virion infectivity factor) protein of HIV an |
| 102 | Regulation of APOBEC3G Function by Vif. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 102) Sheehy AM, Gaddis NC, Malim MH; King's Coll London, UK BACKGROUND: Human T cells possess a natural defense against retroviral invasion. This defense was revealed by the recent discovery of the APOBEC3G/CEM15 gene. The unique anti-viral pathway involving APOBEC3G conveys the ability to effectively resist HIV infection. This enzyme catalyzes the directed and catastrophic dea |
| 103 | HIV Vif: Deactivation of a Deadly Deaminase Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 103) Nathaniel R Landau The Salk Inst for Biological Studies, La Jolla, CA, USA BACKGROUND: HIV-1 Vif blocks the antiviral activity of the cellular cytidine deaminase APOBEC3G/CEM15. The enzyme is encapsilated into Vif-deleted virions where it acts as a potent antiviral. The encapsilated enzyme blocks the virus lifecycle on the next round of infection by catalyzing the conversion of cytosines to u |
| 104 | Host Factors Controlling Species-Specific Replication of Lentiviruses. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 104) Towers GJ; Columbia Univ Coll of Physicians and Surgeons, New York, NY, USA BACKGROUND: Retroviruses are not strictly species specific -- they can jump from one species to another and have done so many times throughout mammalian evolution. When a retrovirus infects a new species it can cause disease, such as HIV/AIDS. Consequently, retroviruses have driven the evolution of dominant mechanisms |
| 105 | Antiviral Protein Targeting Viral RNA Formation. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 105) Goff SP, Gao G, Guo X, Bick MJ, MacDonald M, Rice C; Inst of Microbio, Chinese Academy of Sci, Beijing, China METHODS: To identify novel antiviral activities, we screened mammalian cDNA libraries for genes that prevent infection by a genetically marked retrovirus. Virus-resistant cells were selected from pools of transduced clones, and an active antiviral cDNA was recovered. RESULTS: Expression of the gene caused a profound an |
| 106 | An Independent Analysis of the Effect of Race in VAX004. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 106) Follmann D, Gilbert P, Self S, Hudgens M, Gurwith M, Popovic V, Ackers M, Hu D, Flores J; NIAID, NIH, DHHS, Bethesda, MD, USA Backbround: VAX004, a randomized, double blind, placebo controlled, phase 3 trial of a bivalent rgp120 HIV-1 vaccine showed an overall null result in 5403 volunteers but raised the possibility that vaccine efficacy varied by race. We explored whether the RESULTS in racial subgroups were due to chance or an underlying e |
| 107 | Efficacy of AIDSVAX B/E Vaccines in Injecting Drug Use Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 107 Punnee Pitisutithum Mahidol Univ, Bangkok, Thailand and Bangkok Vaccine Evalution Group BACKGROUND: As a result of HIV/AIDS epidemic in Thailand , a National Plan for HIV/AIDS Vaccine Development and Evaluation was written in 1993. Since then several vaccine studies have been conducted including the phase 3 trial of the AIDSVAX B/E vaccine that began in 1999. METHODS: Following informed consent, 2546 HIV- |
| 108 | Challenges Involved in Eliciting, Neutralizing Antibodies to HIV. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 108) Burton D; The Scripps Res Inst, La Jolla, CA, USA Background and METHODS: The challenges involved in designing immunogens capable of eliciting neutralizing antibodies to HIV will be discussed, with particular emphasis on broadly neutralizing antibodies. The feasibility of eliciting neutralizing antibodies that are potent and broad enough to have some effect upon HIV t |
| 109 | Why An Effective Vaccine for HIV-1 Is Not Currently Within Our Grasp Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 109 Ronald Desrosiers; Harvard Med Sch, New England Primate Res Ctr, Southborough, MA Several lines of evidence indicate that development of an effective vaccine for HIV-1 is going to be, at best, extremely difficult. The inability to solve fundamental scientific questions is the root cause for why a successful vaccine is not currently within our grasp. A renewed, organized, focused effort is needed to |
| 110 | A Randomized, Controlled Trial of PEG-Interferon-alfa-2a plus Ribavirin vs Interferon-alfa-2a plus Ribavirin for Chronic Hepatitis C Virus Infection in HIV-co-infected Persons: Follow-up Results of ACTG A5071 Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 110 R Chung*1, J Andersen2, P Volberding3, G Robbins1, T Liu2, K Sherman4, M Peters3, M Koziel5, B Alston6, D Colquhoun7, T Nevin8, G Harb9, C van der Horst10, and AIDS Clinical Trials Group A5071 Study Team 1Mass Gen. Hosp., Boston, MA, USA; 2Statistical and Data Analysis Ctr. (SDAC), Harvard Sch. of Publ. Hlth., Boston, MA, USA; 3Univ. of California, San Francisco, USA; 4Univ. of Cincinnati, OH, USA; 5Beth Israel Deaconess Hosp., Boston, MA, USA; 6DAIDS, NIAID, NIH, DHHS, Bethesda, MD, USA; 7DMC, FSTRF, Buffalo, NY, USA; 8Social and Sci. Systems, Inc., Rockville, MD, USA; 9Roche Labs., Nutley, NJ, USA; and 10Univ. of North Carolina at Chapel Hill, USA BACKGROUND: Chronic hepatitis C virus (HCV) is a major morbidity in persons infected with HIV. Treatment of HCV in HIV co-infection has been associated with poor responses and frequent intolerability. We conducted the first randomized trial of the efficacy and safety of peginterferon plus ribavirin vs interferon plus r |
| 111 | Relationships between Hepatitis C Virus-specific Immune Responses and Outcomes of Treatment with Interferon and Ribavirin in HIV/HCV Co-infection. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 111) Graham C, Wells A, Liu T, Sherman K, Peters M, Chung R, Andersen J, Koziel M; Beth Israel Deaconess Med. Ctr. and Harvard Med. Sch., Boston, MA, USA BACKGROUND: The relationship between HCV-specific immune responses and outcome of treatment with interferon (IFN) and ribavirin (RBV) is not well defined, but may allow us to better explain patient characteristics associated with treatment effectiveness. We hypothesized that individuals with more vigorous HCV-specific |
| 112 | Final Results of APRICOT: A Randomized, Partially Blinded, International Trial Evaluating Peginterferon-alfa-2a + Ribavirin vs Interferon-alfa-2a + Ribavirin in the Treatment of HCV in HIV/HCV Co-infection Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 112 F J Torriani1, J Rockstroh2, M Rodriguez-Torres3, E Lissen4, J Gonzalez5, A Lazzarin6, G Carosi7, J Sasadeusz8, C Katlama9, J Montaner10, H Sette11, F Duff12, J DePamphilis12, U M Schrenk13, and D Dieterich*14 1Univ. of California, San Diego, USA; 2Univ. of Bonn, Germany; 3Fndn. de Investigación de Diego, Santurce, PR, USA; 4Virgen del Rocío Univ. Hosp., Seville, Spain; 5Hosp. La Paz, Madrid, Spain; 6San Raffaele Vita-Salute Univ., Milan, Italy; 7Univ. of Brescia, Italy; 8Royal Melbourne Hosp., Australia; 9Hosp. Pitié-Salpêtrière, Paris, France; 10Univ. of British Columbia, Vancouver, Canada; 11Inst. de Infectologia Emilio Ribas, Sao Paulo, Brazil; 12Roche, Nutley, NJ, USA; 13Roche, Basel, Switzerland; and 14Mt Sinai Sch. of Med., New York, NY, USA BACKGROUND: The AIDS Pegasys Ribavirin International Co-infection Trial (APRICOT) was designed to evaluate the safety and efficacy of HCV therapies approved for patients with HCV mono-infection in patients with HIV/HCV co-infection. METHODS: We randomized 868 HIV/HCV co-infected subjects in 19 countries to 48 weeks of |
| 113 | Intrahepatic T-cell Responses to Hepatitis C Virus in Patients Co-infected with HCV and HIV prior to anti-HCV Therapy. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 113) Alatrakchi N, Graham CS, Sherman KE, Koziel MJ; Harvard Med. Sch. and Beth Israel Deaconess Med. Ctr., Boston, MA, USA and 2Univ. of Cincinnati, OH, USA BACKGROUND: In patients chronically infected with hepatitis C virus (HCV), whether co-infected or not with HIV, T-cell responses are often undetectable in peripheral blood. We analyzed the strength and specificity of HCV-specific CD8 and CD4 T-cell responses in the liver of HCV/HIV co-infected and HCV mono-infected pat |
| 114 | Frequency of Functional HCV-specific CD8+ Cells Depends on Total CD4+ Counts in HIV-1/HCV Co-infection: Implications for Immune Reconstitution. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 114) Kim AY, Ouchi K, Draenert R, Addo MM, Lucas M, Boczanowski MA, Wurcel AG, McGovern B, Casson D, Chung T, Klenerman P, Walker BD, Lauer GM; Partners AIDS Res. Ctr., Massachusetts Gen. Hosp., Charlestown, USA BACKGROUND: Virus-specific CD8+ cells play an important role in control of both SIV in macaques and HCV in chimpanzees, but no animal model has adequately studied HIV/HCV co-infection. We performed cross-sectional analysis in a large cohort of co-infected humans to determine the effects of HIV on HCV-specific functiona |
| 115 | Hemigenomic Analysis of Hepatitis C Sequence Variation in a Common-Source Outbreak in Relation to Predicted HLA Class I Epitopes. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 115) Ray S, Fanning L, Wang X, Netski D, Thomas D; Johns Hopkins Univ. Sch. of Med., Baltimore, MD, USA and 2Cork Univ. Hosp., Ireland BACKGROUND: Infection with hepatitis C virus (HCV) is an important cause of liver disease both nationally and internationally, disproportionately affecting persons with HIV and AIDS. Advancement in understanding HCV pathogenesis has been hampered by inefficient amplification of large segments of the HCV genome, heterog |
| 116 | DNA Polymorphisms Affect Severity of Disease and Response to Therapy in Subjects Co-infected with HCV and HIV Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11: (abstract No. 116 Peters M, Anderson J, Chung R, Koziel M, Sherman K, Apple R, the ACTG 5071 team, and the NIAID - AIDS Clinical Trials Group, Bethesda, MD; Univ. of California, San Francisco, USA BACKGROUND: Host factors may play a role in the severity of HCV. We aimed to assess the role of DNA polymorphisms in 18 genes (coding region or promoter) involved in inflammation on the severity of HCV and on the response to treatment in HIV/HCV subjects receiving interferon (IFN) or PEG-IFN + ribavirin, in a randomize |
| 117LB | Final Results of ANRS HC02-RIBAVIC: A Randomized Controlled Trial of Pegylated-Interferon-alfa-2b plus Ribavirin vs Interferon-alfa-2b plus Ribavirin for the Initial Treatment of Chronic Hepatitis C in HIV Co-infected Patients Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 117 C Perronne*1, F Carrat2, F Bani-Sadr2, S Pol3, E Rosenthal4, F Lunel5, P Morand6, D Salmon7, G Pialoux8, G Raguin8, C Grillot-Courvalin9, P Cacoub10, and ANRS HC02-RIBAVIC study group; 1CHU Raymond-Poincaré, Garches, France; 2CHU Saint-Antoine, INSERM, Paris, France; 3CHU Necker, Paris, France; 4CHU de l'Archet, Nice, France; 5CHU Hotel-Dieu, Angers, France; 6CHU Michalon, Grenoble, France; 7CHU Cochin, Paris, France; 8CHU Saint-Antoine, Paris, France; 9ANRS, Paris, France; and 10CHU Pitié-Salpétrière, Paris, France BACKGROUND: The need to treat hepatitis C has become a significant issue in HIV-infected subjects. We compared the safety, tolerability, and efficacy of a 48-week course of the standard (IFN-alpha-2b: 3 MIU x 3/week, n = 207) (INF group) to the pegylated (PEG-IFN-alpha-2b: 1.5 -micro/kg x 1/w, n = 205) interferon (PEG |
| 118LB | HCV Resistance to Peg-Interferon/Ribavirin Therapy Is Associated with Increased Immune Activation in HIV/HCV Co-infected Patients. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 118LB) Lempicki RA, Yang J, Dennis G, McLaughlin M, Koratich C, Kleiner D, Kottilil S, Polis MA; SAIC-Frederick, Inc., MD, USA BACKGROUND: HIV-infected patients co-infected with HCV have modest responses to anti-HCV therapy relative HIV-uninfected individuals. The purpose of the study is to examine gene expression patterns in PBMC of HIV/HCV co-infected patients to identify biological processes that distinguish responders from non-responders f |
| 119 | HIV Vaccine Efficacy Trials: Lessons Learned and Future Directions. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 119) Buchbinder S; San Francisco Dept of Publ Hlth, CA, USA BACKGROUND: HIV vaccine efficacy must be evaluated through large clinical trials. Two such efficacy trials have been conducted to date; many lessons can be learned through analysis of these trials. A number of new products have entered clinical testing and may be ready for efficacy evaluation within the next several ye |
| 120 | Tuberculosis and HIV: Is There a Scientific Basis for Hope? Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 120) Small PM; Bill and Melinda Gates Fndn, Seattle, WA, USA BACKGROUND: The challenges in confronting tuberculosis (TB) in the context of HIV are well known to this audience. This plenary talk will address the question, Is there a scientific basis for hope in understanding why TB is so problematic and for how to improve the situation, either by preventing or treating tuberculos |
| 121 | Mutations in p6 Gag Associated with Alterations in Replication Capacity in Drug Sensitive HIV-1 Are Implicated in the Budding Process Mediated by TSG101 and AIP1. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 121) Bates M, Chappey C, Parkin N; ViroLogic Inc., South San Francisco, CA, USA BACKGROUND: HIV-1 utilizes a network of host vacuolar sorting proteins to bud from the infected cell. Viral budding requires interactions between the gag protein p6 and several cellular proteins, Tsg101 and AIP1, mediated by specific amino acid motifs in p6, PT/SAP and LYP, LRSL, respectively. The Replication Capacity |
| 122 | Identification of a Gene Product, Murr1, that Restricts HIV-1 Replication in Primary Resting CD4+ T-lymphocytes. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 122) Ganesh L, Burstein E, Guha-Niyogi A, Louder MK, Mascola JR, Klomp LW, Wijmenga C, Duckett CS, Nabel G; Vaccine Res. Ctr., NIAID, NIH, DHHS, Bethesda, MD, USA BACKGROUND: Although HIV-1 infects quiescent and proliferating CD4+ lymphocytes, the virus replicates poorly in resting T cells. Factors that block viral replication in these cells may help to prolong the asymptomatic phase of HIV infection; however, the molecular mechanisms that control this process are not fully unde |
| 123LB | De Novo Latent Infection of Quiescent CD4+ T Cells in the Absence of Exogenous Stimuli. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 123LB) O'Doherty U, Baytop C, Yu J, Swiggard W; Univ. of Pennsylvania, Philadelphia, USA BACKGROUND: Resting CD4+ T cells comprise the best defined reservoir of HIV-1 latent infection, but how these reservoirs are formed is unclear. One hypothesis is that latent reservoirs form when activated T cells are infected as they return to a resting state. Another hypothesis is that CD4+ T cells receive some transi |
| 124LB | HIV Infection of Naturally Occurring and Genetically Reprogrammed Human Regulatory T Cells. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 124LB) Oswald-Richter K, Grill SM, Shariat N, Leelawong M, Sundrud MS, Unutmaz D; Vanderbilt Univ. Med. Sch., Nashville, TN, USA BACKGROUND: A T-cell subset, defined as CD4+CD25+ (Treg cells), was recently shown to suppress T-cell activation. Because Treg cells express CD4, they are potential targets of HIV in vivo. However, the role of Treg cells during HIV infection remains unknown. Here we tested the susceptibility of, both naturally occurrin |
| 125 | Sequence Determinants in the gp120 V1-V4 Region Modulate Susceptibility to Neutralization by Autologous and Pooled Plasma. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 125) Derdeyn C, Decker J, Bibollet-Ruche F, Mokili J, Muldoon M, Heil M, Kasolo F, Musonda R, Allen S, Hahn BH, Shaw G, Korber BT, Hunter E; Univ. of Alabama at Birmingham, USA BACKGROUND: We recently defined the properties of viruses present in 8 heterosexual donor-recipient pairs near the time of transmission. Viruses that established infection uniformly exhibited shorter length and fewer N-linked glycosylation (N-gly) sites in the gp120 V1-V4 region; limited sequence divergence as evidence |
| 126 | Decreased Survival of B Cells of HIV-Viremic Patients Mediated by Altered Expression of Receptors of the TNF Superfamily. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 126) Moir S, Malaspina A, Donoghue E, Vasquez J, Chun TW, Planta M, Pickeral O, Birse C, Fauci AS; NIAID, NIH, DHHS, Bethesda, MD, USA and 2Human Genome Sci. Inc., MD, USA BACKGROUND: In previous studies we identified perturbations in B cells of HIV-viremic patients that were consistent with activation-induced terminal differentiation, including loss of CD21 expression in association with decreased proliferation, increased immunoglobulin secretion, and appearance of plasma cell-like morp |
| 127 | Mechanism(s) Responsible for the Immunodeficiency Induced by Highly Pathogenic SHIV and SIV Appear to Be Fundamentally Different. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 127) Igarashi T, Endo Y, Nishimura Y, Buckler C, Sadjadpour R, Donau O, Dumaurier MJ, Plishka R, Buckler-White A, Martin M; NIAID, NIH, DHHS, Bethesda, MD, USA and 2Weill Med. Coll. of Cornell Univ., New York, NY, USA BACKGROUND: In contrast to SIV, which induces immunodeficiency over a 1- to 3-year period, highly pathogenic SHIV causes an irreversible and systemic depletion of CD4+ T lymphocytes in rhesus monkeys within weeks of infection. Nonetheless, the seemingly more aggressive SHIV has proven to be easier to control by the sam |
| 128 | Frequent Simian Retrovirus Infection in Persons Occupationally Exposed to Nonhuman Primates. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 128) Switzer WM, Shanmugam V, Bhullar V, Yee J, Lerche N, Parekh B, Cong M, Boneva R, Chapman LE, Folks TM, Heneine W; CDC, Atlanta, GA, USA and 2Univ. of California, Davis, USA BACKGROUND: The recognition that AIDS originated as a zoonosis heightens concerns associated with human infection with simian retroviruses endemic in nonhuman primates, including simian immunodeficiency virus (SIV), simian type D retrovirus (SRV), simian T-cell lymphotropic virus (STLV), and simian foamy virus (SFV). A |
| 129 | Modeling T-cell Labeling with BrdU in SIV-infected Sooty Mangabeys. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 129) Ribeiro RM, Mascio MD, McClure HM, Johnson RP, Kaur A, Perelson AS; Univ. of Oxford, UK BACKGROUND: Sooty mangabeys are natural hosts of the simian immunodeficiency virus (SIV) that do not progress to AIDS despite sustained high viral loads. Understanding the dynamics of T-lymphocyte turnover in these animals may shed light on the mechanisms of CD4+ T-cell depletion in HIV-infected humans and SIV-infected |
| 130 | Th1-type SIV-specific Cellular Immune Responses Targeting Structural Proteins Are Consistently Detected in Naturally SIV-infected Sooty Mangabeys. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 130) Wang ZC, McClure HM, Kaur A; New England Regional Primate Res. Ctr., Harvard Med. Sch., Southborough, MA, USA and 2Yerkes Natl. Primate Res. Ctr., Emory Univ., Atlanta, GA, USA BACKGROUND: Sooty mangabeys are natural hosts of the simian immunodeficiency virus (SIV) and do not manifest with AIDS despite sustained high viral loads. In contrast to pathogenic lentiviral infection, neither increased T-lymphocyte turnover nor increased immune activation is detected in SIV-infected sooty mangabeys, |
| 131 | Stop Study: After Discontinuation of Efavirenz, Plasma Concentrations May Persist for 2 Weeks or Longer Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 131 S Taylor*1, S Allen2, S Fidler3, D White1, S Gibbons4, J Fox3, J Clarke3, J Weber3, P Cane5, A Wade2, E Smit5, and D Back4 1Birmingham Heartlands Hosp. and Univ. of Birmingham, UK; 2Coventry and Warwickshire Hosp., UK; 3Imperial Coll. London & St. Marys Hosp., UK; 4Univ. of Liverpool, UK; and 5HPA, Birmingham Heartlands Hosp., UK BACKGROUND: Current antiretroviral drugs differ in their relative plasma elimination half -lives (t1/2). The reported t1/2 of EFV is 40 to 55 hours; therefore EFV concentrations may persist at therapeutic levels for greaterlonger than 1 week following discontinuation. If drugs with a shorter half-life t1/2 are stopped |
| 132 | Relationships between Efavirenz Pharmacokinetics, Side Effects, Drug Discontinuation, Virologic Response, and Race: Results from ACTG A5095/A5097s Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 132 H Ribaudo*1, D Clifford2, R Gulick3, C Shikuma4, K Klingman5, S Snyder6, and E Acosta7 1Harvard Sch. of Publ. Hlth., Boston, MA, USA; 2Washington Univ., St. Louis, MO, USA; 3Cornell Univ., New York, NY, USA; 4Univ. of Hawaii, Honolulu, USA; 5DAIDS, NIAID, NIH, DHHS, Bethesda, MD, USA; 6Social and Sci. Systems, Inc., Silver Spring, MD, USA; and 7Univ. of Alabama at Birmingham, USA BACKGROUND: Central nervous system (CNS) side effects occur commonly with efavirenz (EFV). We assessed the relationship of EFV pharmacokinetics, side effects, drug discontinuation, virologic response, and patient characteristics. METHODS: ACTG A5095 is a double-blind clinical trial of initial antiretroviral therapy, i |
| 133 | A Common CYP2B6 Variant Is Associated with Efavirenz Pharmacokinetics and Central Nervous System Side Effects: AACTG Study NWCS214 Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 133 D Haas*1, H Ribaudo2, R Kim1, C Tierney2, G Wilkinson1, R Gulick3, D Clifford4, T Hulgan1, and E Acosta5 1Vanderbilt Univ., Nashville, TN, USA; 2Statistical and Data Analysis Ctr. (SDAC), Harvard Sch. of Publ. Hlth., Boston, MA, USA; 3Weill Med. Coll. of Cornell Univ., New York, NY, USA; 4Washington Univ., St. Louis, MO, USA; and 5Univ. of Alabama at Birmingham, USA BACKGROUND: EFV is metabolized by CYP2B6, a polymorphic hepatic mixed function oxidase. Functional differences in CYP2B6 activity have been identified in vitro, but their clinical relevance is uncertain. These include a G-to-T change at position 516 (G516T) that identifies CYP2B6 *6 and *7 haplotypes. CNS side effects |
| 134 | Lopinavir Inhibitory Quotient Predicts Virologic Response in Highly Antiretroviral-experienced Patients Receiving High-dose Lopinavir/Ritonavir Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 134 R Bertz*1, J Li1, M King1, D Kempf1, D Podzamczer2, C Flexner3, C Katlama4, D V Havlir5, S Letendre6, J Eron7, L Weiss8, J Gatell9, A Simon4, K Robinson1, and S Brun1 1Abbott Labs., Abbott Park, IL, USA; 2Hosp. de Bellvitge, Barcelona, Spain; 3Johns Hopkins Univ. Sch. of Med., Baltimore, MD, USA; 4Hosp. de la Pitie-Salpetriere, Paris, France; 5Univ. of California, San Francisco, USA; 6Univ. of California, San Diego, USA; 7Univ. of North Carolina at Chapel Hill, USA; 8Hosp. Europeen George Pompidou, Paris, France; and 9Hosp. Clin., Barcelona, Spain Background: In patients failing multiple ARV regimens, increased doses of lopinavir/ ritonavir (LPV/r) may achieve higher LPV concentrations relative to HIV phenotypic susceptibility, thus overcoming certain levels of LPV resistance. The purpose was to assess predictors of antiviral response in patients receiving high- |
| 135 | Unexpected Complexity in Nuclear Receptor Activation by HIV Protease Inhibitors and Induction of CYP Enzymes and Transporters. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 135) Marzolini C, Tirona RG, Lee W, Gervasini G, Ho RH, Leake BF, Kim RB; Vanderbilt Univ. Sch. of Med., Nashville, TN, USA BACKGROUND: Drug-drug interactions remain an important cause of morbidity and mortality associated with HIV drug therapy. Recent studies have shown that activation of certain regulatory proteins, called adopted orphan nuclear receptors--such as the pregnane X receptor (PXR), constitutive androstane receptor (CAR), and |
| 136LB | Effect of Ribavirin on Intracellular and Plasma Pharmacokinetics of Nucleoside Reverse Transcriptase Inhibitors in Patients With HCV/HIV Co-infection: Final Results of a Randomized Clinical Study Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 136LB J-M Gries*1, F J Torriani2, M Rodriguez-Torres3, V Soriano4, M J Borucki5, P Piliero6, E Lissen7, M Sulkowski8, K Wang1, D Dieterich9, and D Back10 1Roche, Nutley, NJ, USA; 2Univ. of California, San Diego, La Jolla, USA; 3Fndn. de Investigacion de Diego, Santurce, Puerto Rico; 4Inst. de Salud Carlos III, Madrid, Spain; 5Univ. of Texas Hlth. Ctr., Tyler, USA; 6Albany Med. Coll., NY, USA; 7Virgen del Rocío Univ. Hosp., Seville, Spain; 8Johns Hopkins Univ. Sch. of Med., Baltimore, MD, USA; 9Mt. Sinai Sch. of Med., New York, NY, USA; and 10Univ. of Liverpool, UK BACKGROUND: Whether ribavirin interferes with the pharmacokinetics of antiretroviral drugs is an important, but unanswered question relevant to the treatment of HCV in HIV-infected persons. Our objective was to examine the effect of RBV on intracellular phosphorylation of zidovudine (ZDV), |
| 137 | Tolerance and Potent Anti-HIV-1 Activity of Reverset following 10 Days of Mono-therapy in Treatment-naïve Individuals Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 137 R L Murphy*1, D Schürmann2, A Beard3, L Cartee3, R F Schinazi4, and M J Otto3 1Northwestern Univ., Chicago, IL, USA; 2Charité Univ. Hosp., Berlin, Germany; 3Pharmasset, Inc., Tucker, GA, USA; and 4Emory Univ. Sch. Med. and VA Med. Ctr., Atlanta, GA, USA BACKGROUND: Reverset (RVT, D-D4FC) is a NRTI with specific and potent in vitro activity against HIV-1 isolates resistant to AZT , 3TC , and other NRTI. In a single dose phase 1 study, the pharmacokinetic data were linear with dose from 25 to 200 mg and resulted in a 0 |
| 138 | Pharmacological Evaluation of a Dual Deoxycytidine Analogue Combination: 3TC and SPD754 Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 138 R Bethell*1,4, J Adams1,2, J De Muys3,4, J Lippens3,4, A Richard4, B Hamelin4, C Ren4, P Collins4, C Struthers-Semple3, T Holdich3, and J Sawyer2 1PharmaRes., Morrisville, NC, USA; 2Prism Ideas Ltd., Nantwich, UK; 3Shire Pharm. Devt., Basingstoke, UK; and 4Shire Biochem Inc., Laval, Canada BACKGROUND: PD754 is a deoxycytidine analogue with activity against HIV-1, including isolates resistant to other available NRTI. SPD754 and 3TC have additive antiviral activity against wild-type HIV-1 in vitro, but share a common intracellular anabolic pathway. In vitro studies were conducted to investigate the effects |
| 139 | Single and Multiple Dose Escalation Study to Investigate the Safety, Pharmacokinetics, and Receptor Binding of GW873140, a Novel CCR5 Receptor Antagonist, in Healthy Subjects Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 139 J Demarest1, K Adkison1, S Sparks1, A Shachoy-Clark1, K Schell1,2, S Reddy1, L Fang1, K O'Mara1, S Shibayama3, and S Piscitelli*1 1GlaxoSmithKline, Research Triangle Park, NC, USA; 2Univ. of Wisconsin, Madison, USA; and 3ONO Pharm. Ltd., Osaka, Japan BACKGROUND: GW873140 is a novel CCR5 receptor antagonist that binds specifically to human CCR5 and demonstrates potent in vitro anti-HIV activity. GW873140 binds to human CCR5 with a unique profile as evidenced by the selective inhibition of monoclonal antibody binding. METHODS: A double blind, randomized, placebo-cont |
| 140LB | SCH D: Antiviral Activity of a CCR5 Receptor Antagonist Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 140LB D Schurmann1, R Rouzier2, R Nougarede2, J Reynes3, G Fatkenheuer4, F Raffi5, C Michelet6, A Tarral7, C Hoffmann8, J Kiunke8, H Sprenger9, J vanLier10, A Sansone11, M Jackson11, and M Laughlin*11; 1Clin. Res./Charite Hosp., Berlin, Germany; 2CentreCap, Montpellier, France; 3CHU Gui De Chauliac, Montpellier, France; 4Univ. of Cologne, Germany; 5Nantes Med. Univ., France; 6Univ. Hosp. of Rennes, France; 7Biotrial, Rennes, France; 8Univ. of Kiel, Germany; 9Univ. Hosp. Groningen, The Netherlands; 10PharmaBioResearchGroup BV, Groningen, The Netherlands; and 11SPRI, Kenilworth, NJ, USA BACKGROUND: SCH C and SCH D are orally bioavailable CCR5 receptor antagonists with potent in vitro antiviral activity. SCH D has greater in vitro potency with mean IC90 values approximately 5- to 10-fold lower than SCH C. The in vivo antiviral activity of SCH C has been previously demonstrated when administered to subj |
| 141 | Antiviral Activity, Safety, and Tolerability of a Novel, Oral Small-molecule HIV-1 Attachment Inhibitor, BMS-488043, in HIV-1-infected Subjects a Novel, Oral Small-Molecule HIV-1 Attachment Inhibitor, BMS-488043, in HIV-1-Infected Subjects Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 141 G Hanna*1, J Lalezari2, J Hellinger3, D Wohl4, T Masterson1, W Fiske1, J Kadow1, P Lin1, M Giordano1, R Colonno1, and D Grasela1 1Bristol-Myers Squibb Co., Princeton, NJ, USA; 2Quest Clin. Res., San Francisco, CA, USA; 3Community Res. Initiative of New England, Boston, MA, USA; and 4Univ. of North Carolina at Chapel Hill, USA BACKGROUND: BMS-488043 is a novel, oral small-molecule attachment inhibitor of HIV-1 that blocks viral entry by preventing the binding of the viral envelope protein gp120 to cellular CD4 receptors. Potent and selective inhibition is observed in vitro against macrophage-, T-, and dual-tropic HIV-1. Phase I studies in he |
| 142 | Herpes Simplex and the Global Epidemiology of HIV. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 142) Celum C; Univ of Washington, Seattle, USA BACKGROUND: Increasing evidence demonstrates a substantial link between the epidemics of sexually transmitted HIV-1 and HSV-2 infection. More than 30 epidemiologic studies have demonstrated that prevalent HSV-2 is associated with increasing the risk of HIV-1 acquisition from 2- to 4-fold. Per-sexual contact transmissio |
| 143 | Interaction of HIV and Malaria. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 143) Steketee R; CDC, Atlanta, USA BACKGROUND: Globally, HIV and malaria are among the leading causes of morbidity and mortality, and their geographic overlap, particularly in sub-Saharan Africa, is striking. METHODS: We reviewed available information collected since the mid 1980s to evaluate the impact of HIV and malaria on each other. We examined evid |
| 144 | Influence of Socioeconomic and Political Situation on the Distribution of HIV-1 Variants in the Democratic Republic of Congo. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 144) Vidal N, Mulanga C, Bazepeo SE, Kasali Mwamba J, Tshimpaka J, Kashi M, Mama N, Valea D, Delaporte E, Lepira F, Peeters M; UR36, Inst of Res. and Devt., Montpellier, France BACKGROUND: We studied the dynamics of HIV-1 subtype distribution in the Democratic Republic of Congo (DRC), characterized by low and stable HIV prevalence, high genetic diversity of HIV-1, and unfavorable socioeconomic and unstable political situations over the last decade. METHODS: Blood samples were collected in 200 |
| 145 | Identification and Genomic Sequence of an HIV-1 Group N Isolate from Cameroon. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 145) Bodelle P, McArthur CP, Vallari A, Coffey R, Yamaguchi J, Devare SG, Beyeme M, Brennan CA; Abbott Labs., Abbott Park, IL, USA BACKGROUND: HIV-1 group N is a rare strain that has only been found in Cameroon where it is estimated to account for |
| 146 | Is Bacterial Vaginosis a Cause or a Consequence of HIV Infection? Studies from Rakai, Uganda. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 146) Gray RH, Wawer MJ, Kiwanuka N, Sewankambo N, Kigozi G, Quinn TC, Wabwire-Mangen F, Kiddugavu M, Lutalo T, Serwadda D; Johns Hopkins Univ., Bloomberg Sch. Of Publ. Hlth., Baltimore, MD, USA BACKGROUND: Bacterial vaginosis has been associated with HIV in prospective and cross-sectional studies. To determine whether bacterial vaginosis is a risk factor for HIV acquisition, or wether HIV infection exacerbates disturbances of vaginal flora, we assessed data from a cohort in Rakai, Uganda . METHODS |
| 147 | Effect of Antiretroviral Therapy on Tuberculosis in Patients with AIDS in Rio de Janeiro, Brazil. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 147) Pacheco AG, Golub JE, Lauria LM, Cavalcante SC, Moore RD, Moulton L, Chaisson RE, Durovni B; Hlth. Secretariat of the City of Rio de Janeiro, Brazil BACKGROUND: Tuberculosis (TB) is an important complication of HIV infection in Brazil and other developing countries. Brazil provides combination antiretroviral therapy (ART) free of charge to all patients who meet clinical criteria, and maintains an extensive clinic and laboratory system for the appropriate prescripti |
| 148 | One Year of HAART in Mozambique: Survival, Virological, and Immunological Results of DREAM Project in Adults and Children. Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11: (abstract No. 148 Palombi L, Narciso P, Perno CF, Mancinelli S, Guidotti G, Ceffa S, Erba F, Liotta G, Germano P, Barreto A, Gialloreti LE, Vella S, Marazzi MC; Univ. of Tor Vergata, Rome, Italy BACKGROUND: Since February 2002 the DREAM program, run in Mozambique by the Community of Sant Egidio in the frame of public health sector, provided HIV+ patients free-of-charge both HAART and immune-virological monitoring. METHODS: Until August 2003, 802 HIV+ adults (510 female) and 215 children were included in the co |
| 149 | The Pruritic Papular Eruption of HIV in Uganda Is Most Commonly a Reaction to Insect Bites. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 149) Resneck J Jr, Van-Beek M, Furmanski L, Machtinger E, Oyugi J, LeBoit P, Maurer T, Berger T, Kambugu F, Katabira E; Univ. of California, San Francisco, USA BACKGROUND: A major cause of HIV-related morbidity in sub-Saharan Africa is a commonly occurring, intensely pruritic rash previously labeled the pruritic papular eruption of HIV. The rash consists of abundant hyperpigmented papules and nodules, and the resulting scars are disfiguring and stigmatizing. The prevalence of |
| 150 | Genital Expression of Human Papillomavirus Infections in Women with HIV: Predicting Incidence of Vulvar Warts and Vulvar Neoplasia and the Course of Grade 1 Cervical Intraepithelial Neoplasia. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 150) Massad LS, Silverberg M, Springer G, Evans C, Passaro DJ, Strickler HD, Hessol N, Darragh TM, Palefsky J, Levine A, Sacks HS, Anastos K, Minkoff H, Watts DH; Southern Illinois Univ. Sch. of Med., Springfield, USA BACKGROUND: This multicenter prospective cohort study (October 1994 to September 2002) determined incidence and predictors of genital warts and vulvar intraepithelial neoplasia (VIN) and defined rates of progression and regression of grade 1 cervical intraepithelial neoplasia (CIN1) among women with HIV. Study. METHODS |
| 151 | Effects of Testosterone Administration in HIV-infected Women with Low Weight: A Randomized, Placebo-controlled Study Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 151 S Dolan*, S Wilkie, N Aliabadi, M Sullivan, N Basgoz, B Davis, and S Grinspoon Massachusetts Gen. Hosp., Boston, USA BACKGROUND: HIV disease is increasing among women, many of whom remain symptomatic with low weight and poor functional status. Although androgen levels may often be reduced in such patients, the safety, tolerability, and efficacy of testosterone administration in this population remains unknown. METHODS: In this double |
| 152 | Gender Differences in Progression to AIDS and Death from HIV Seroconversion in a Cohort of Intravenous Drug Users from 1986 to 2001. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 152) Hera M, Ferreros I, Amo J, Olalla P, Muga R, Romero J, Guerrero R, Hernandez-Aguado I, Perez-Hoyos S; Univ. Miguel Hernandez, Alicante, Spain BACKGROUND: Consensus is that gender does not influence HIV progression. However, ongoing substance abuse or co-morbid diseases among HIV-infected injecting drug users (IDU) influence a number of other health outcomes, including AIDS survival and mortality. We studied gender differences in HIV progression to AIDS and d |
| 153 | Polymorphisms in the Gene Encoding for CX3CR1 Are Important Determinants of HIV-1-related Disease Progression of Children. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 153) Singh K, Hughes M, Chen J, Spector SA; Univ. of California, San Diego, USA and 2Harvard Sch. of Publ. Hlth., Boston, MA, USA BACKGROUND: CX3CR1, the receptor for the chemokine, fractalkine, is a minor co-receptor of HIV-1 and is thought to modulate the immune response to viral infections. The effect of CX3CR1 polymorphisms on HIV-1 pathogenesis is controversial with conflicting reports on its role in disease progression in HIV-1-infected adu |
| 154 | Prognostic Markers of Survival in HIV-infected Children in the CHAP Trial, Zambia. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 154) Sinyinza F, Mulenga V, Lishimpi K, Bhat G, Chintu C, Casbard A, Walker S, Farrelly L, Kaganson N, Nunn A, Gibb D; Univ. Teaching Hosp., Lusaka, Zambia on behalf of the CHAP Trial and 2MRC Clin. Trials Unit, London, UK on behalf of the CHAP Trial BACKGROUND: There are few longitudinal data on the natural history of pediatric HIV infection in Africa. METHODS: Children with HIV Antibiotic Prophylaxis (CHAP) is a randomized controlled trial comparing daily cotrimoxazole with placebo in HIV-infected children aged 1 to 14 years in Lusaka. Baseline information includ |
| 155 | Mortality among Infected and Uninfected Infants Born to HIV-infected Women in Africa: Infants, HIV, and Mortality in Africa Study. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 155) Newell ML; Inst. of Child Hlth., Univ. Coll. London, UK BACKGROUND: All children, irrespective of HIV-infection status, of HIV-infected mothers may be at increased risk of death; in infected children, age at infection acquisition may be associated with mortality risk. Using individual data from 7 randomized clinical MTCT intervention trials we estimated mortality in childre |
| 156LB | A Randomized Placebo-controlled Trial of Cotrimoxazole as Prophylaxis against Opportunistic Infections in Children with HIV-1 Infection in Zambia. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 156LB) Mulenga V, Gibb D, Bhat G, Walker A, Sinyinza F, Lishimpi K, Farrelly L, Chileshe R, Kaganson N, Mwenya D, Mwansa J, Zumla A, Gillepsie S, Nunn A, Chintu C; Univ. Teaching Hosp., Lusaka, Zambia BACKGROUND: No trials have reported on the efficacy of cotrimoxazole prophylaxis for adults or children with HIV in areas of high levels of bacterial resistance to the drug. METHODS: Children with HIV Antibiotic Prophylaxis (CHAP) is a randomized trial comparing daily cotrimoxazole (240 mg until 5 years, then 480 mg) w |
| 157 | Blockade of Attachment and Fusion Receptors Inhibits HIV-1 Infection of Human Cervical Tissue. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 157) Hu Q, Watts P, Frank I, Williams V, Moore J, Pope M, Shattock R; St. George's Hosp. Med. Sch., London, UK BACKGROUND: The majority of HIV-1 infection occurs via mucosal exposure, with heterosexual transmission as the predominant mode of infection worldwide. However, the early events of HIV-1 entry and transmission are still poorly understood. Identification of cellular factors governing sexual transmission of HIV-1 is crit |
| 158 | Intravaginal PSC-RANTES Protects against Vaginal Transmission of SHIV162P to Macaques; Implications for HIV Microbicide Strategies and Pathogenesis. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 158) Veazey R, Offord R, Hartley O, Blauvelt A, Dufour J, Piatak M Jr, Lifson J, Mosier D, Lederman MM; Tulane Natl. Primate Res. Ctr., Covington, LA, USA BACKGROUND: Despite years of research, no cure or effective vaccine for HIV infection currently exists. This has led to the push for strategies that could prevent HIV infection, such as microbicides, that could be applied to the vagina and protect women from infection. However, compounds that damage or destroy the lipi |
| 159 | Cellulose Acetate Phthalate Protects Macaques from Multiple, Low-dose Vaginal Exposures with an SHIV Virus: New Strategy to Study HIV Pre-clinical Interventions in Non-human Primates. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 159) Otten RA, Adams DR, Kim CN, Jackson E, Pullium JK, Lee K, Grohskopf L, Monsour M, Jivani N, Serbinova E, Butera ST, Folks TM; CDC, Atlanta, GA, USA BACKGROUND: A nonhuman primate model for HIV-1 infection that more closely mimics sexual transmission by repeated low-dose exposure is critical to better understand and design intervention strategies using microbicides or vaccines. METHODS: Here we describe such an in vivo system using female pig-tailed macaques infect |
| 160 | Propelling Future Advances in HIV/AIDS Therapeutics through Basic Discovery. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 160) Greene WC; Gladstone Insat of Virology and Immunology, Univ of California, San Francisco, USA BACKGROUND: The natural history of HIV infection has been fundamentally altered by the introduction of powerful antiviral drugs targeting the reverse transcriptase and protease gene products of HIV. Many HIV-infected patients are now living longer and enjoying a higher quality of life because of these drugs. However, t |
| 161 | Host Genetics and Pharmacogenetics: Implications for Clinical Practice Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 161) Amalio Telenti Ctr Hosp Univ Vaudois, Lausanne, Switzerland BACKGROUND: Since completion of the human genome, research efforts have aimed at gathering information on the basis of genetic diversity by building databases of single nucleotide polymorphisms, common DNA sequence variations among individuals (The SNP Consortium) and defining a haplotype map (The HapMap) of the human |
| 162 | Important Interactions between Drug Resistance Mechanisms: Implications for Therapy Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 162) Lisa M Demeter Univ of Rochester Sch of Med and Dentistry, NY, USA Twenty antiretroviral drugs, representing 4 different drug classes, are currently approved for clinical use in the US. Because of the extremely large number of potential drug combinations, it is impossible to rigorously compare the outcomes of all possible antiretroviral regimens in clinical trials. Therefore, it is es |
| 163 | The Future of Antiretroviral Therapy: What If There Is No Vaccine? Conf Retrovir Opportunistic Infect 2004 Feb 8-11;11: (abstract No. 163) Schooley RT; Univ of Colorado Hlth Sci Ctr, Denver, USA BACKGROUND: It has been 20 years since the initial promise of an AIDS vaccine in two years by then Health and Human Services Secretary Margaret Heckler. During this time we have learned a tremendous amount about the epidemiology, transmission efficiency, and immunobiology of HIV-1. During this period, investigations ha |
| 164 | Cross-subtype Immune Responses of HIV-1 Group M Consensus Env Immunogens. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 164) Weaver EA, Lu Z, Li Y, Liao HX, Ma B, Alam MS, Scearce RM, Sutherland L, Decker JM, Hartman Z, Amalfitano A, Shaw GM, Korber BT, Hahn BH, Montefiori DC, Haynes BF, Gao F; Duke Univ. Med. Ctr., Durham, NC, USA BACKGROUND: The high level of genetic variation in HIV-1 represents a major obstacle for AIDS vaccine development. To decrease the genetic distance between candidate immunogens and field virus strains, we have generated a group M consensus env gene (CON6) that is equidistant from any subtype or recombinant viruses. Thi |
| 165 | Broad HIV-1 Sensitivity to Neutralization with Vaccine Sera, Monoclonal Antibodies, and HIV+ Plasma and Sera Is a Pan-gp160 Phenomenon Associated with High Fusion Activity and Shortened V1/V2 Rregions. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 165) Wrin T, Chappey C, Huang W, Petropoulos C; ViroLogic Inc., South San Francisco, CA, USA BACKGROUND: Broad HIV-1 neutralization sensitivity, including susceptibility to vaccine sera, has generally been limited to lab strain viruses such as NL43 or MN, or R5 viruses with long in vitro passage histories such as SF162 and BAL. Primary viruses with minimal in vitro cell culture history are much more difficult |
| 166 | Containment of SIV Replication in Rhesus Macaques by Vaccine-induced Cytotoxic T Lymphocytes. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 166) Matano T, Kobayashi M, Igarashi H, Takeda A, Sugiura W, Mori K, Kano M, Iida A, Hasegawa M, Miyazawa M, Yasunami M, Kimura A, O'Connor D, Watkins D, Nagai Y; Univ. of Tokyo, Japan BACKGROUND: Virus-specific cytotoxic T lymphocytes (CTL) play an important role in the control of immunodeficiency virus infections. Recently, several CTL-based AIDS vaccine trials in macaques showed control of replication of SHIV89.6P that induces acute AIDS. However, it is becoming increasingly clear that SHIV89.6P m |
| 167 | Enhanced Envelope Incorporation in Pseudovirions Produced by Co-transfection with Codon-optimized Envelope Genes. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 167) Kothe DL, Chertova E, Li Y, Zammit KP, Decker JM, Korber BT, Shaw GM, Lifson JD, Hahn BH; Univ. of Alabama at Birmingham, USA BACKGROUND: HIV-1 particles have been shown to contain small amounts of envelope glycoprotein on their surface, which may affect their immunogenicity in vivo. Higher levels of envelope glycoprotein incorporation into particle-based immunogens may improve neutralizing antibody responses in vaccinated individuals. METHOD |
| 168 | Evaluation of 2 Therapeutic HIV Vaccination Regimens in HAART-treated Primary HIV Infection Subjects following Analytical Treatment Interruption: QUEST PROB3005, a Randomized, Placebo-controlled Study. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 168) Kinloch S, Perrin L, Hoen B, Lampe F, Phillips A, Goh L, Tsoukas C, Sonnerborg A, Autran B, Andersson J, Habib RE, Theofan G, Carter N, Cooper D; Royal Free and Univ. Coll. Med. Sch., London, UK BACKGROUND: It has been hypothesized that therapeutic vaccination of HAART-treated primary HIV infection subjects could induce long-term suppression of plasma HIV-1 RNA (pVL) following HAART discontinuation. This randomized, double-blind, placebo-controlled trial was conducted to assess the effect of therapeutic HIV va |
| 169 | Randomized, Placebo-controlled, Phase1/2a Evaluation of the Safety, Biological Activity and Antiretroviral Properties of an Avipox Virus Vaccine Expressing HIV gag-pol and Interferon-gamma in HIV-1 Infected Subjects. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 169) Cooper D, Workman C, Puls R, Bloch M, Baker D, Bodsworth N, Anderson J, Crowe S, French M, Hoy J, Kelleher A, Aichelberg A, Ward L, Law M, Emery S; Natl. Ctr. in HIV Epidemiology and Clin. Res., Sydney, Australia BACKGROUND: A multi-centre, randomized, double-blind, placebo-controlled trial examined the safety, immunogenicity and biological activity of candidate HIV vaccines using recombinant fowlpox virus (rFPV) vectors. METHODS: HIV-infected patients who commenced combination antiretroviral therapy (ART) at primary HIV infect |
| 200 | Novel and Promiscuous CD8+ T-cell Epitopes in Conserved Regions of Subtype C Gag Recognized by HIV-1-infected Southern Africans. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 200) Masemola A, Khoury G, Mashishi T, Paximadas M, Puren A, Gray C; Natl. Inst. for Communicable Diseases, Johannesburg, South Africa BACKGROUND: Recognition of HLA class I-restricted epitopes by Gag-specific cytotoxic T lymphocytes (CTL) has been shown to be important in the control of HIV-1 replication in acute infection. We report the identity of novel and previously defined epitopes in Gag restricted by HLA alleles commonly expressed in southern |
| 201 | Maintenance and Expansion of Mucosal CD8+ CTL in HIV-1 Infection. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 201) Ding Y, Cao J, Galloway C, Berger D, McNevin JP, Diaz G, Nelson P, McElrath MJ; Fred Hutchinson Cancer Res. Ctr., Seattle, WA, USA and 2Univ. of Washington, Seattle, USA BACKGROUND: Cytotoxic T lymphocytes (CTL) residing in the genital and rectal mucosa may play a key role in controlling local viral replication and reducing HIV-1 transmission. METHODS: In our previous studies, we demonstrated that mucosal CTL can have similar epitope specificities and MHC restriction patterns as those |
| 202 | Beyond Help: Direct Effector Functions of HIV-1-Specific CD4+ T Cells. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 202) Norris P, Moffett H, Yang O, Kaufmann D, Addo M, Walker BD, Rosenberg E; Massachusetts Gen. Hosp., Boston, MA, USA and 2Geffen Sch. of Med., Univ. of California, Los Angeles Med. Ctr., USA. BACKGROUND: Robust p24-specific proliferative responses are associated with control of HIV viremia, but direct mechanistic evidence on the role of virus-specific CD4+ T cells has been lacking. In vitro CD4+ T-cell cytolytic activity is seen in a number of viral infections in humans including HIV, Epstein-Barr virus, |
| 203 | Identification of Circulating Antigen-specific CD4+ T Lymphocytes with a CCR5+, Cytotoxic Phenotype in an HIV-1 Long-term Non-progressor, and in CMV Infection. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 203) Zaunders J, Dyer W, Wang B, Munier ML, Newton R, Moore J, Miranda-Saksena M, Mackay C, Cooper DA, Saksena NK, Kelleher AD; St. Vincent's Hosp., Sydney, Australia BACKGROUND: Antigen-specific CD4+ T cell responses are believed to be most important in providing optimal help for B cell antibody synthesis and CD8+ cytotoxic T cells. In most cases of HIV-1 infection, antigen-specific CD4+ T cells have been difficult to identify using standard in vitro techniques. One possibility is |
| 204 | Cytokine Profiles of T-cell Responses Induced by Vaccines and Natural Infection. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 204) De Rosa SC, Perfetto SP, Bailer R, Lamoreaux L, Koup R, Roederer M; Vaccine Res. Ctr., NIAID, NIH, DHHS, Bethesda, MD, USA BACKGROUND: Identification and characterization of the responses induced soon after vaccination that will ultimately correlate with vaccine efficacy will help to speed vaccine development. T cell responsiveness is commonly determined by in vitro stimulation with antigenic proteins or peptides followed by assaying for a |
| 205 | Evaluation of an Antigen-recognizing CD8+ T-cell Population: Relevance of CD4dimCD8bright T Cells to HIV Pathogenesis. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 205) Zloza A, Connick E, Landay A, Al-Harthi L; Rush Univ. Med. Ctr., Chicago, IL, USA and 2Univ. of Colorado Hlth. Sci. Ctr., Denver, USA BACKGROUND: A potent cytotoxic T-cell response is associated with better HIV-1 control. Our group and others have identified a subpopulation of mature CD8+ T cells that express CD4 dimly on their surface. This T-cell phenotype is up-regulated as much as 60% in response to activation. CD4dimCD8bright cells constitute up |
| 206 | Phospho-proteomic Flow Cytometry Signatures of HIV-1 Infection Reveals Early Perturbations in T Cell Activation. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 206) Fortin JF, Nolan GP; Baxter Lab. for Genetic Pharmacology, Stanford Univ., CA, USA BACKGROUND: It has been suggested that HIV-1 infection alters the signaling environment of the host cell. It is expected that such alterations aid in HIV-1 pathogenesis by either debilitating cellular function(s) or by enabling HIV-1 replication processes. For instance, early after infection by HIV-1, T cells are found |
| 207 | Antigenic Presentation by HIV-1 Bearing Peptide-Loaded Class II Major Histocompatibility Complex (MHC) Molecules Induces NF-kB and NFAT in Human CD4+ T Lymphocytes. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 207) Roy J, Martin G, Giguere JF, Belanger D, Petrin M, Bounou S, Tremblay MJ; Laval Univ., Ste-Foy, Canada BACKGROUND: It is well documented that a wide range of host-derived molecules are incorporated in the envelope of human immunodeficiency virus type 1 (HIV-1) and either modify HIV-1 infectivity or initiate signaling events in T cells. The aim of the present study is to evaluate if HIV-1 could incorporate peptide-loaded |
| 208 | Expansions of Distinct Vbeta Populations in HIV Infected Patients Do Not Secrete IFN-gamma ex vivo after Stimulation with HIV Peptides. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 208) Meyer-Olson D, Altfeld M, Brady KW, Dranert R, Allen TM, Addo MM, Strick D, Rosenberg ES, Walker BD, Kalams SA; Partners AIDS Res. Ctr., Massachusetts Gen. Hosp., Harvard Med. Sch., Boston, USA BACKGROUND: In HIV-infected individuals perturbations of the CD8+ T cell repertoire, with expansion of distinct Vbeta-subpopulations, have been discussed to be HIV specific and might reflect an immunological dysfunction of the HIV specific CD8+ T-cell response. It has been hypothesized that these expansions might repre |
| 209 | Modulation of CTL Differentiation by Cell Division. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 209) Yu J, Chen HY, Cano J, Reichman R, Jin X; Univ. of Rochester, NY, USA BACKGROUND: Recent studies indicate that the incomplete differentiation of HIV-specific CTL is associated with the lack of virologic control in chronic HIV infection, and that CTL proliferation potential is positively associated with protective immunity in both mice and humans. We hypothesize that the incomplete differ |
| 210 | Heterogeneity of Functionally Distinct Populations of CD8 T Cells in Human Virus Infections. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 210) Zimmerli SC, Harari A, Vallelian F, Pantaleo G; Lab. of AIDS Immunopathogenesis, Lausanne, Switzerland BACKGROUND: Studies performed in mice have shown that a substantial proportion of memory CD8 T cells persisting after the clearance of antigen have the ability to secrete IL-2 in addition to IFN-gamma. The wide heterogeneity of CD8 T-cell responses has been proposed to be dependent upon the type of the pathogen in huma |
| 211 | The Ratio of CD28 Expression on CD4+ T-cells to HLA-DR CD38 Expression on CD8+ T-cells Is a Predictor of Functional Immune Responses in Chronic HIV-1-infection. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 211) Lange C, Valdez H, Sieg S, Gibney J, Rodriguez B, Medvik K, Asaad R, Lederman M; Ctr. for AIDS Res., Case Western Reserve Univ., Cleveland, OH, USA and Med. Clin., Res. Ctr. Borstel, Germany BACKGROUND: Increased proportions of anergic (CD28-) CD4+ T-cells and activated (HLA-DR+ CD38+) CD8+ T-cells are related to disease progression in HIV-1 infection. As these indices may reflect different determinants of immune function we investigated whether the ratio of CD28+ CD4+ T-cells to HLA-DR+ CD38+ CD8+ T-cells |
| 212 | Generation of Dysfunctional CD8+ T Cells in the Setting of HIV Infection. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 212) Favre D, Stoddart C, Hoh R, Martin J, Deeks S, McCune JM; Gladstone Inst. of Virology and Immunology, San Francisco, CA, USA and 2Univ. of California, San Francisco, USA BACKGROUND: HIV infection can result both in depletion of CD4+ T cells and in the generation of dysfunctional CD8+ T cells. We have previously shown that HIV infection of predendritic cells type 2 in the thymus induces the secretion of IFN-a, which causes MHC-I upregulation on thymocytes and thymic epithelial cells. In |
| 213 | Increased Immune Activation Is Associated with Decreased Responsiveness to in vivo IL-2 Administration. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 213) Sereti I, Sklar P, Ramchandani M, Natarajan V, Metcalf J, Wynne S, Davey R, Kovacs J, Lane HC; NIAID, NIH, DHHS, Bethesda, MD, USA BACKGROUND: Intermittent administration of IL-2 to HIV infected patients leads to expansion of the CD4 T cell pool in the majority of patients with CD4 counts >200 cells/ul, by improving survival of CD4 T cells. A lower baseline and nadir CD4 cell count have been associated with lower responses to IL-2. The mechanisms |
| 214 | Viral Infection Persistence but not Level of Virimia Leads to Ablation of HIV-Specific CD4 and CD8 T Cells. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 214) Yassine-Diab B, Kernaleguen AE, Younes S, Boulassal R, Rouleau D, Routy JP, Tremblay C; Univ. of Montreal, Quebec, Canada BACKGROUND: Several studies provide strong evidence that CD4+ Th cells play a critical role in determining the persistence of memory and effector CTL in viral infections. HIV-specific CD4+ and CD8+ T cells are maintained in LTNP and in individuals treated with HAART suggesting the presence of a strong memory T-cell com |
| 215 | Diminished CD4+ Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 215) Speelmon E, Desbien A, Livingston-Rosanoff D, McElrath MJ; Univ. of Washington, Seattle, USA and 2Fred Hutchinson Cancer Res. Ctr., Seattle, WA, USA BACKGROUND: Rare individuals report repeated unprotected sexual exposures to HIV-1, yet remain seronegative and appear to resist infection with the virus. We investigated the possibility that reduced in vitro CD4+ |
| 216 | Selective Loss of IL-2 Production by HIV-specifiic T Cells Correlates with Loss of Viral Control in an Adolescent Cohort. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 216) Kapogiannis B, Henderson S, Robinson H, Amara R; Emory Univ., Atlanta, GA, USA BACKGROUND: We are developing a cohort of adolescents with sexually acquired HIV-1 infection who are either HAART-treated or untreated to temporally characterize the frequency, function, and phenotype of their cellular immunity. The goal for developing the cohort is to learn more about cellular immune responses in infe |
| 217 | Gag-specific Memory CTL Responses and Antiretroviral Drugs Act in Synergy to Control HIV-1 Replication in Infected Children. Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 217) Buseyne F, Lechenadec J, Burgard M, Mayaux MJ, Rouzioux C, Blanche S, Riviere Y Inst. Pasteur, Paris, France BACKGROUND: Effect of antiretroviral treatment on the HIV-specific CD8+ T lymphocytes has been extensively investigated in adults, but it less well characterized in children. The prognostic value of the HIV-specific cellular immune response on treatment outcome has not been addressed so far. The aim of the present stud |
| 218 | HIV Infection Affects TCR CDR3 Vbeta Repertoire in CD4 CD45RA T Lymphocytes in Children. Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 218) Yin L, Kou ZC, Goodenow MM, Sleasman JW; Univ. of Florida Coll. of Med., Gainesville, USA and 2All Children's Hosp., Univ. of South Florida, St. Petersburg, USA BACKGROUND: HIV infection results in significant perturbation of T-cell receptor (TCR) CDR3 V( families within CD8 CD45RA and CD45RO T-cell subsets. The extent of TCR disruption within CD45RA CD8 T cells correlates with high virus load and advanced immune suppression. This study evaluates the impact of infection on CD4 |
| 219 | Higher HIV-1 Gag IFN-gamma Responses Observed among Black Children Infected with HIV-1. Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 219) Sharp ER, Karlsson RK, Barbour JD, Jordan KA, Sandberg JK, Wiznia A, Rosenberg MG, Nixon DF; Gladstone Inst. of Virology and Immunology, Univ. of California, San Francisco, USA BACKGROUND: The course of AIDS progression and levels of HIV plasma viremia are known to be different between racial groups. This may be related to immune response, and immune response genes may differ in frequency or type by ethnic group. There have been only a limited number of studies comparing immune responsiveness |
| 220 | A Minority of HLA-B Alleles Dominate the Anti-C Clade HIV-specific Cytotoxic T Lymphocyte Response Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 220) Kiepiela P, Mngqundaniso N, Day C, Ramduth D, Addo MM, Chetty P, Nene N, Ntumba N, Brander C, Harlow J, Henry C, Honeyborne I, Altfeld M, Walker BD, Goulder PJ; HIV Pathogenesis Prgm., Univ. of Natal, Durban, South Africa BACKGROUND: HIV disease progression varies substantially among individuals. Some of this variation may be explained by differential expression of particular HLA class I molecules and the contribution these alleles may make to the anti-HIV CTL response. To analyze the relative contribution of individual HLA class I mole |
| 221 | Immunodominance of HLA-A*1101-restricted HIV-specific CD8+ T-cell Responses in Thai Patients Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 221) Hansasuta P, Ruangdachsuwan S, Buranapraditkun S, Ruxrungtham K, Rowland-Jones SL; Chulalongkorn Univ., Bangkok, Thailand and 2Oxford Univ., UK BACKGROUND: HIV-1 infection is probably the most important public health problem in many countries, including Thailand . Development of an effective HIV vaccine undoubtedly needs essential information on immune correlate to protection. HIV-specific cytotoxic T lymphocytes (CTL) responses are believed to play an importa |
| 222 | Quantifiable, HIV-specific CTL Responses Explain HLA-related Risk of Progression to AIDS. Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 222) Scherer A, Oxenius A, Price DA, Guenthard HF, Hirschel B, Phillips RE, McLean A Swiss HIV Cohort Study, Oxford Univ., UK BACKGROUND: There are significant associations between certain class I HLA alleles and the rate of progression to AIDS after infection with HIV. We present new data providing an explanatory mechanism for this relationship. METHODS: A large study of structured treatment interruptions yielded cross-sectional and longitud |
| 223 | Population Genetics of Rural Rainforest Inhabitants In Cameroon with High HIV-1 Genetic Diversity Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 223) Torimiro J, Carr J, Wolfe N, Karachi P, Kim B, Mpoudi E, Birx D, Burke D, Carrington M; London Sch. of Hygiene and Tropical Med., UK BACKGROUND: Genetic variability is a hallmark of HIV and is particularly pronounced in Cameroon where the greatest diversity of HIV-1 is reported. In other populations, mutations in HIV-1 co-receptors (CCR2 and CCR5) and the co-receptor ligand (SDF-1) can influence susceptibility to HIV-1 and disease progression, as ca |
| 224 | A Novel Escape Mutation in HLA B27 Positive Individuals Infected with HIV-1 Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 224) Ammaranond P, Bockel D, Zaunders J, Satchell C, Guerin J, Cooper D, Kelleher A; Natl. Ctr. in HIV Epidemiology and Clin. Res., Univ. of New South Wales, Sydney, Australia and 2St. Vincent's Hosp., Sydney, Australia BACKGROUND: HLA B27 is associated with long-term non-progression (LTNP). The immune response in HLA B27+ HIV-1-infected individuals is characterised by an immunodominant response to a conserved epitope KRWIILGLNK in p24 Gag (a.a. 263-272). Variation from arginine at position 2 in an HLA B27-restricted epitope always ha |
| 225 | CD8+ T-cell Responses Directed against an Immunodominant HIV-1 Epitope Cross-restricted by HLA Alleles Associated with Different Effect on Disease Progression are Defined by Differential TCR Vbeta Usage Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 225) Yu XG, Meyer-Olson D, Lichterfeld M, Perkins B, Kim AY, Johnston M, Parta M, Wurcel AG, Alter G, Allen T, Kalams SA, Addo MM, Walker BD, Altfeld M; Partners AIDS Res. Ctr., Boston, MA, USA and 2AIDS Prgm., Bellevue Hosp. Ctr., New York, NY, USA BACKGROUND: Some HLA class I alleles (HLA-B*27, B*51, B*57, A*11) and CD8+ T-cell responses restricted by them, have been associated with slow HIV-1 disease progression. Functional differences in CD8+T-cell responses specific for epitopes cross-presented by alleles associated with different effect on disease progressio |
| 226 | Differences in T-cell Responses against HIV Epitopes may Explain Associations of Certain HLA Class I Alleles with Disease Progression Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 226) Sabbaj S, Bansal A, Yusim K, Kaslow R, Tang J, Mulligan M, Korber BT, Wilson C, Goepfert P; Univ. of Alabama at Birmingham, USA and 2Los Alamos Natl. Lab., NM, USA BACKGROUND: The reasons underlying the association of certain HLA class I alleles with different rates of HIV disease progression remain poorly understood. To determine if differences in the immune response to different epitopes explain the associations, we compared the responses between HLA*B35/53 and B*57 known for t |
| 227 | Evidence for Thymic Function in HIV-infected Adults Following Sustained Suppression of Chronic HIV Infection Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 227) Poulin JF, Harris JM, Higuera-Alhino D, Gotway M, McCune JM; Gladstone Inst. of Virology and Immunology, San Francisco, CA, USA and 2Univ. of California, San Francisco, USA BACKGROUND: After the initiation of effective antiretroviral therapy, most HIV-infected patients demonstrate an increased number of naïve phenotype and total CD4+ T cells in the peripheral blood. Previous studies investigating the role of the thymus in such immune reconstitution have relied upon some but not all of the |
| 228 | Intensification of Antiretroviral Treatment in Subjects with Long-term Viral Suppression Does Not Lead to Substantial Improvement in Residual Immune Deficits or Significant Reduction in HIV-1 Latent Reservoir Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 228) Smith KY, Valdez H, Aga E, Bosch RJ, Connick E, Clax P, Rooney J, Landay A, Patterson B, Siliciano R, Lederman M, for the ACTG a5136 Protocol Team; Rush Univ. Med. Ctr., Chicago, IL, USA BACKGROUND: Patients who start HAART during moderately advanced HIV disease exhibit residual immune abnormalities despite adequate viral load control. These abnormalities do not appear to improve with continued HAART. Our objective was to ascertain whether antiretroviral (ARV) intensification in patients with controlle |
| 229 | Presence of Higher Numbers of HIV-specific Late Effector CD8+ T cells in Patients Partially Controlling Multi-drug Resistant Virus and in Long-term Non-progressors Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 229) Emu B, Moretto WJ, Hoh R, McCune JM, Nixon DF, Deeks S; Univ. of California, San Francisco, USA and 2Gladstone Inst. of Virology and Immunology, San Francisco, CA, USA BACKGROUND: One hypothesis of T-cell dysfunction is abnormal maturation of HIV-specific cells. We have seen that some antiretroviral-treated patients with multidrug-resistant HIV maintain low-level viremia and have robust HIV-specific CD4+ and CD8+ T-cell responses.Given these observations, we hypothesize that these pa |
| 230 | Quantitative CD38 Expression on CD8 T Cells as a Predictor of CD4 T-cell Maintenance among Patients Failing Salvage Antiretroviral Therapy Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 230) Goicoechea M, Miller C, Spina C, Currier J, Kemper C, Witt M, Leedom J, Forthal D, Keiser P, McCutchan A, Richman D, Haubrich R, and the California Collaborative Treatment Group (CCTG); Univ. of California, San Diego, USA BACKGROUND: CD38 is a lymphocyte surface marker of immune activation. High expression of CD38 on CD8 lymphocytes is a predictor of decline in CD4 cell count independent of plasma HIV-1 viral load. With viral control during antiretroviral therapy (ARV) CD38 expression declines, but does not reach levels seen in uninfect |
| 231 | Efficacy of and Immunologic Responses to Influenza Vaccine in HIV-1-infected Patients: A Prospective Study Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 231) Yamanaka H, Teruya K, Tanaka M, Honda M, Gatanaga H, Genka I, Tachikawa N, Kikuchi Y, Hirabayashi Y, Gotanda T, Suzuki Y, Kimura S, Oka S; Intl. Med. Ctr. of Japan, Tokyo and 2Kitasato Inst. Res. Ctr. for Biologicals, Tokyo, Japan BACKGROUND: Influenza vaccine is generally recommended to HIV-1 infected persons. However, efficacy or immunologic responses of the vaccine have been reported in small studies. We, therefore, prospectively evaluated the efficacy of and immunologic responses to the vaccine in 328 HIV-1 infected patients. METHODS: Consec |
| 232 | ACTG 5015: Naïve T-cell Reconstitution is Associated with Immune Activation Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 232) Kalayjian R, Landay A, Pollard R, Pu M, Spritzer J, Tebas P, Gross B, Valcour V, Cu-Uvin S, Fiscus S, Fidel P, Wu A, Fox L, Stocker V, Lederman M AIDS Clinical Trials Group Protocol 5015; MetroHlth. Med Ctr, Cleveland, OH, USA BACKGROUND: Naïve T cells, thought to represent key immunologic reserves, are often depleted in HIV disease. Immune activation may play an important role in this deficiency. The goal of this study was to identify correlates of naïve CD4 and CD8 cell numbers before treatment and after 48 weeks of HAART. METHODS: ACTG 50 |
| 233 | Persistent Anti-HIV CD4+ T Cell Lymphoproliferative Responses Result in no Suppressive Effect on the Level of Viral Rebound after Treatment Interruption in Chronically HIV-1-infected "Blippers" Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 233) Papasavvas E, Kostman J, Pistilli M, Thiel B, Mackiewicz A, Foulkes A, Gross R, Jordan K, Sandberg J, Nixon D, Gallo C, Ondercin J, Schmidt L, Mounzer K, Montaner L; Wistar Inst., Philadelphia, PA, USA BACKGROUND: CD4+ and CD8+ anti-HIV T cell responses are hypothesized to be factors associated with control of HIV-1 replication. A lack of T helper response has been proposed as a limiting factor to the efficacy of antiviral CD8 responses. METHODS: An observational cohort of 14 chronically HIV-1-infected patients on AR |
| 234 | Survey of HIV-specific Immune Responses in HAART-naïve, HIV+ Subjects in the Chronic Phase of Infection Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 234 Peretz Y, Alter G, Makedonas G, Tsoukas CM, Bernard NF; McGill Univ., Montreal, Canada and 2Massachusetts Gen. Hosp., Boston, USA BACKGROUND: HIV-specific T-cell responses appear early in HIV infection and are believed to be important in controlling viremia in untreated infection. We present here results generated using an interferon-gamma (IFN-gamma) ELISpot assay to screen for responses to all expressed HIV genes in typical treatment naïve HIV |
| 235 | Suppression of HIV-1 Replication with Antiretroviral Therapy during Chronic Infection Is Associated with Broadening of HIV-1 p24-specific CD4+ T-cell Epitope Recognition Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 235 Boritz E, Palmer B, Wilson CC; Univ. of Colorado Hlth. Sci. Ctr., Denver, USA BACKGROUND: Immune control of HIV-1 replication may fail in part due to progressive dysfunction and depletion of HIV-1-specific CD4+ T cells. To investigate whether viral suppression on antiretroviral therapy (ART) helps reverse HIV-1-specific CD4+ T cell defects during chronic infection, we determined the frequency, e |
| 236 | Viral Rebound after Discontinuing Antiretroviral Treatment is Influenced by HIV Nef-specific CD8+ T-cell Responses Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 236 Lopez M, Benito JM, Barreiro P, Soriano V; Hosp. Carlos III, Madrid, Spain BACKGROUND: The role of the cytostatic agent hydroxyurea (HU) in the treatment of HIV infection remains controversial. A significant proportion of patients switched to didanosine ( ddI ) plus HU as maintenance therapy after prolonged viral suppression with H |
| 237 | T-cell Responses to HIV and Opportunistic Pathogens Following Patient Initiated Interruption of Antiretroviral Treatment Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 237 Schrier R, Letendre S, Durand D, McCutchan JA, Res Ctr VN, Ellis R; Univ. of California, San Diego, USA BACKGROUND: The consequences of antiretroviral treatment interruption remain controversial. Temporary exposure to HIV antigens may boost immune responses to HIV. However, increased virus production and circulation could also seed new viral reservoirs and sequester or deplete helper T lymphocytes. METHODS: Twelve subjec |
| 238 | Immunologic Determinants of Failure in Individualized Structured Treatment Interuptions. Should the Timing of HAART be Reconsidered? Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 238 Maggiolo F, Ripamonti D, Trabattoni D, Quinzan G, Gregis G, Schenal M, Clerici M, Suter F; Hosp. Riuniti, Bergamo, Italy and 2Univ. Med. Sch., Milan, Italy BACKGROUND: Structured treatment interuptions are a possible strategy in long-term HIV infection management. METHODS: We evaluated individualized, immunologically driven structured treatment interuptions in a prospective, randomized study (BASTA) of 114 patients on an effective ARV therapy (HIV-RNA |
| 239 | Restoration of CD4+ T-cell Responses to Cytomegalovirus is Short-lived in Severely Immunodeficient HIV Patients Responding to Highly Active Antiretroviral Therapy Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 239 French MA, Keane NM, Stone SF, Price P, Lee S, Almeida C, James I Royal Perth Hosp., Australia BACKGROUND: The use of HAART in severely immunodeficient HIV patients co-infected with cytomegalovirus ( CMV ) usually results in increased CMV-specific CD4 T-cell responses but it is unclear how long they persist. We have measured CMV-specific CD4 T-cell responses using 3 different assays over 5 years of HAART. |
| 240 | 32-Week Period of Suppressive Antiretroviral Therapy Fails to Reconstitute Innate Immunity Parameters Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 240 Azzoni L, Chehimi J, Farabaugh M, Herman C, Mounzer K, Kostman J, Montaner LJ; Wistar Inst., Philadelphia, USA BACKGROUND: Cross-sectional studies have shown that innate immunity effectors [Natural Killer (NK) cells, plasmacytoid and myeloid Dendritic Cells (PDC, MDC] are depleted and impaired in viremic HIV+ individuals. Here we address the longitudinal changes in innate immunity effectors in HIV+ patients initiating ART and m |
| 241 | Differential Effect of HAART during Acute HIV infection on HIV-specific CD4+ T-cell Proliferative Capacity and Function Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 241 Jansen C, Cuyper ID, Steingrover R, Jurriaans S, Prins J, Baarle D, Miedema F; Sanquin Res., Academic Med. Ctr., Univ. of Amsterdam, The Netherlands and 2Academic Med. Ctr. and Intl. Antiviral Therapy Ctr., Amsterdam, The Netherlands BACKGROUND: CD4+ T cell help is thought to play an important role in an effective CTL response against HIV. However, a decrease in function of HIV-specific CD4+ T cells has been shown during HIV infection. In chronic infection, this effect cannot be reversed using highly active anti-retroviral therapy (HAART). Nonethel |
| 242 | Identification of a Novel Immunodominant CD4+ T-lymphocyte Epitope and Characterization of the MHC Class II Restriction Using SIV Gag-specific CD4+ T-cell Line from Rhesus Macaques Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 242 Abdel-Motal UM, Johnson RP; New England Primate Res. Ctr., Harvard Med. Sch., Southborough, MA, USA METHODS: In the present study, rhesus macaque infected with the attenuated viruses were screened for CD4+ T-cell responses against Gag protein using overlapping peptides spanning the entire Gag protein. A novel CD4+ T-cell epitope and its restriction MHC class II molecules were identified. To define and to map in detai |
| 243 | Depletion of CD4hiCD8low Effector Memory T Lymphocytes in SIV-infected Rhesus Macaques Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 243 Macchia I, Gauduin MC, Kaur A, Johnson RP; Inst. Superiore di Sanita, Rome, Italy and 2New England Primate Res. Ctr., Harvard Med. Sch., Southborough, MA, USA BACKGROUND: Circulating T lymphocytes co-expressing CD4+ and CD8+ have been described in the peripheral blood of humans and several animal species. However, the origin and functional properties of CD4+CD8+ T cells remain poorly understood. METHODS and RESULTS: We identified 2 distinct populations of CD4+CD8+ T cells in |
| 244 | Assessment of gamma delta T Cells in Normal and SIVsmm-infected Sooty Mangabeys Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 244 Zhou D, Milush J, Torres J, Sodora D;;;Univ. of Texas Southwestern Med. Ctr., Dallas, USA BACKGROUND: Sooty mangabeys naturally infected with SIVsmm do not exhibit AIDS-related clinical symptoms. Our laboratory is interested in identifying the immune components playing key roles in keeping mangabeys from progressing to simian AIDS. The focus of this study is to determine the potential role that gdT cells se |
| 245 | NKT Cells Are Preserved in Patients Beginning HAART during Acute Infection Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 245 Vasan S, Siladji E, Hogan C, Hurley A, Markowitz M, Tsuji M;;;Aaron Diamond AIDS Res. Ctr., Rockefeller Univ., New York, NY, USA BACKGROUND: Natural killer T-cells (NKT) are a subset of lymphocytes which share features of T cells and natural killer cells, and bridge the innate and adaptive immune response. They are rapidly depleted during HIV-1 infection despite the use of HAART in chronically infected individuals. We sought to determine whether |
| 245 | Skewed Expression of CD81 in CD4 T Lymphocytes and NK Cells during HIV-1 Infection Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 246 Meroni L, Milazzo L, Galazzi M, Mazzucchelli R, Mologni D, Morelli P, Menzaghi B, Moroni M, Galli M, Riva A;;; Univ. of Milan, Italy BACKGROUND: CD81 is a trans-membrane protein and was shown to bind hepatitis C virus envelope 2 protein. CD81 cross-linking enhances anti-CD3 activation of T cells in regard to IFN-g production and is required for maintainance of a T-helper response necessary to preserve strong CTL function. Cross-linking of CD81 block |
| 247 | Reconstitution of NK Cell Cytotoxic Function in HIV Infection: Effects of Viral Load and Circulating DC Subsets Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 247 Chehimi J, Azzoni L, Farabaugh M, Shawver L, Mounzer K, Kostman J, Montaner LJ;;; Wistar Inst., Philadelphia, PA, USA BACKGROUND: Dendritic Cells (DC) and NK cells are important effectors of the innate immune response. Bi-directional cross-talk between the two cell types provides a powerful NK cell activation or a control mechanism for DC function (control switch). We have previously shown an impairment in DC and NK frequencies and fu |
| 248 | Functional and Phenotypic Characterization of Natural Killer Cell Subsets in HIV Infection Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 248 Alter G, Malenfant J, Yu X, Lichterfeld M, Walker BD, Altfeld M;;; Massachusetts General Hosp., Charlestown, MA, USA BACKGROUND: The course of HIV disease is variable among infected subjects. Several genetic markers, including specific HLA class I and II alleles, are highly associated with differential disease progression. More recent findings suggest a strong association between natural killer (NK) inhibitory receptor (KIR) genotype |
| 249 | IL-7 Down-regulates Surface Expression of IL-7Ralpha in vitro and in vivo Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 249 Sasson S, Zanetti G, Zaunders J, Mallon P, Cooper D, Kelleher A;;; Natl. Ctr. in HIV Epidemiology and Clin. Res., Univ. of New South Wales, Sydney, Australia and 2St. Vincent's Hosp., Sydney, Australia BACKGROUND: Interleukin-7 (IL-7) is crucial in the extra-thymic maintenance of the naïve CD4+ T-cell subset. IL-7 acts via the IL-7 receptor (IL-7R) which consists of a specific (-chain (CD127) dimerised to the cytokine common (-chain (CD132). Plasma levels of IL-7 are elevated in HIV-1 infection and inversely correlat |
| 250 | Cytokine Receptor Expression and IFN-gamma Production in Cord Blood Mononuclear Cells: alpha-CD3 Stimulation Elicits a Change in IL-7Ralpha Expression, but Does Not Induce Production of IFN-gamma Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 250 Aroniadis OC, Pahwa R, McCloskey T, Pahwa S;;; North Shore-LIJ Res. Inst., Manhasset, NY, USA BACKGROUND: We have previously shown that addition of exogenous cytokines IL-2 , -7, and -15 augment HIV-gag specific IFN-g responses in pediatric HIV-infected patients. We tested the hypothesis that the immunological responses of naïve T cells can be augmented by re-stimulation and/or addition of exogenous cytokine. |
| 251 | Interleukin-7 Receptor Expression on Thymocytes at Different Stages of Maturation and the Effect of IL-7, TNF-alpha and HIV Infection Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 251 Young CD, Angel JB;;;Ottawa Hlth. Res. Inst., Ontario, Canada BACKGROUND: HIV infection is associated with impaired thymic function, which, based on in vitro studies appears to occur at an early stage of thymocyte development. IL-7, through interactions with the IL-7 receptor (CD127), plays a significant role in the intrathymic maturation of immunocompetent T cells. Since CD127 e |
| 252 | High Numbers of Functional Pre-Dendritic Cells Type 2 Are Maintained in Patients with Non-Progressive HIV Disease Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 252 Beaumont T, Hoh R, Deeks S, McCune JM;;; Gladstone Inst. of Virology and Immunology, San Francisco, CA, USA and 2Univ. of California, San Francisco, USA BACKGROUND: The immunologic parameters associated with modulation of HIV disease progression remain unclear. Human (pre-dendritic cells type 2 (preDC2) are effector cells of the innate immune system, producing protective mediators such as IFN-g immediately upon contact with viruses such as HIV and then migrating into d |
| 253 | Detection of a Natural Released Form of Soluble DC-SIGN in Human Dendritic Cell Cultures Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 253 Butera S, Li J, Jia H, Blyveis N, Wilson C;;; CDC, Atlanta, GA, USA and 2Univ. of Colorado Hlth. Sci. Ctr., Denver, USA BACKGROUND: DC-SIGN is a C-type lectin highly expressed on immature dendritic cells (DCs) that can bind HIV-1 gp120 and mediate infection of CD4+ T cells. RNAs encoding putative soluble forms of DC-SIGN have been identified. However, naturally occurring production of soluble DC-SIGN, which could influence mucosal trans |
| 254 | Short-term Flt3L Treatment Effectively Mobilizes Functional Macaque Dendritic Cells Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 254 Teleshova N, Jones J, Kenney J, Purcell J, Bohm R, Gettie A, Pope M;;; Population Council, Ctr. for Biomed. Res., New York, NY, USA BACKGROUND: In vivo administration of soluble Flt3L increases dendritic cell (DC) numbers to favor improved DC-targeting of vaccine antigens and augmented vaccine efficiency. In addition to confirming the effectiveness of human Flt3L in macaques, we strove to determine the optimal regimen to elevate numbers of function |
| 255 | SDF-1/CXCL12 Production by Dendritic Cells Decreases Infection of Lymphocytes by X4 Strains in the Immune Synapsis Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 255 Gonzalez N, Bermejo M, Pablos JL, Baleux F, Arenzana F, Alcami J;;; Inst. de Salud Carlos III, Madrid, Spain BACKGROUND: HIV infection of lymphocytes is enhanced by the DC-SIGN molecule present in dendritic cells. However, emergence of X4 HIV strains occurs late in the course of HIV infection, suggesting that a selective pressure interpheres with the switch from CCR5 to CXCR4 co-receptor tropism. We hypothesized that SDF-1 pr |
| 256 | Correlates of Resistance to HIV-1 Infection in Homosexual Men with High-risk Sexual Behavior Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 256 Koning FA, Jansen CA, Dekker J, Dukers N, Prins M, Baarle D, Schuitemaker H;;; Sanquin Res., Univ. of Amsterdam, The Netherlands and 2Municipal Hlth. Svc., Univ. of Amsterdam, The Netherlands BACKGROUND: Some individuals remain HIV-seronegative despite high-risk exposure to the virus. METHODS: We studied 29 homosexual men from the Amsterdam Cohort with high-risk sexual behavior for possible correlates of HIV-1 resistance. As controls we used pre-seroconversion (pre-SC) samples from HIV negative homosexual m |
| 257 | Alpha-Defensin 1, 2, and 3 Expression is Upregulated in HIV+ Lymphoid Tissue, but Relatively Deficient in Lymphoid Follicles Where Virus Replication Predominates Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 257 Folkvord J, Connick E;;; Univ. of Colorado Hlth. Sci. Ctr., Denver, USA BACKGROUND: Alpha-defensins 1, 2, and 3 (AD), which are produced primarily in neutrophils, have been demonstrated to exert antiretroviral activity in vitro. In HIV-1-infected individuals, AD have been reported to be released by CD8+ T-cells from long-term nonprogressors and to be associated with monocytes as well. To a |
| 257b | Protective Effect of Natural Killer Cell Immunoglobulin Receptors Associated with HIV-1 Transmission and Disease Progression in the Chicago Multiple Aids Cohort Study Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 257b Trachtenberg EA, Sollars C, Korber B, Hayes EA, Erlich HA, Wolinsky S, Kepler T;;; Children's Hosp. & Res. Ctr., Oakland, CA, USA BACKGROUND: Killer cell immunoglobulin receptors (KIR) are regulatory molecules that control the cytolytic activity of natural killer (NK) cells. NK cells are components of the innate immune system s early response to viral agents, functioning to produce cytokines or to destroy infected cells. In association with their |
| 258 | Comparison between Sendai Virus and Adenovirus Vectors in Induction of HIV-1 Genes into Human Dendritic Cells Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 258 Hosoya N, Miura T, Kawana-Tachikawa A, Shioda T, Odawara T, Nakamura T, Kitamura Y, Kano M, Kato A, Hironaka T, Hasegawa M, Nagai Y, Iwamoto A;;; Advanced Clin. Res. Ctr., Inst. of Med. Sci., Univ. of Tokyo, Japan BACKGROUND: Immuno-genetherapy using dendritic cells can be applied to HIV-1 infection. We compare the efficiency of a new viral vector based on Sendai virus (SeV) with adenovirus vector (AdV). METHODS: Dendritic cells (DC) were obtained from human monocytes cultured with IL-4 and GM-CSF for 7 days. DC were infected wi |
| 259 | Multimeric Soluble CD40 Ligand as a Potent DNA Vaccine Adjuvant Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 259 Stone GW, Kee K, Barzee S, Snarsky V, Richman D, Yu XF, Kornbluth R;;; Univ. of California, San Diego, USA and 2John Hopkins Sch. of Hygiene and Publ. Hlth., Baltimore, MD, USA BACKGROUND: CD40 ligand (CD40L, CD154), a potent endogenous activator of humoral and cellular immunity, is a member of the TNF superfamily (TNFSF) that includes RANKL, 4-1BBL, CD27L/CD70, and GITRL. A soluble trimeric form of CD40L has already been tested in vaccines, but recent data indicate that CD40L and other TNFSF |
| 260 | CD4-Dependent, Non-APC Mediated Antigen Presentation Pathway: a Novel Pathogenetic Mechanism of Chronic HIV Infection Is Corrected by Therapeutic Vaccination Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 260 Lisziewicz J, Xu J, Trocio J, Whitman L, Bakare N, Lewis M, Lori F;;; Res. Inst. for Genetic and Human Therapy (RIGHT), Washington, DC, USA and 2Bioqual, Inc., Rockville, MD, USA BACKGROUND: HIV elicits vigorous immune responses enduring several years, however, infection is not cleared. We tested the hypothesis that CD4, and not antigen presenting cells (APC), are presenting the antigen inappropriately to CD8 cells, and therapeutic vaccination specifically targeting APC corrects this aberrant p |
| 261 | Human Dendritic Cells Transduced by Attenuated Bacteria Carrying a DNA Vaccine Vector Can Present Viral Antigens to Autologous T Cells in vitro Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 261 Gurner D, Huang Y, Dhodapkar K, Ho DD;;; Aaron Diamond AIDS Res. Ctr., New York, NY, USA and 2Rockefeller Univ., New York, NY, USA BACKGROUND: The promise of DNA vaccination is limited in part by invasive, untargeted administration. We have previously proposed a means of improving the strategy by using attenuated Salmonella typhimurium to deliver plasmids directly to APC. Here we demonstrate that human DC transduced by the bacteria to express vira |
| 262 | Foamy Viruses as Potential Vectors for HIV Vaccine and Gene Therapy Applications Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 262 Hardy WD, Liu C, Xie Y, Folks T, Chen IS;;; Los Angeles, CA, USA and 2Atlanta, GA, USA BACKGROUND: Foamy viruses (FV) are retroviruses endemic in nonhuman primates and other vertebrates but not in humans. Persistent FV infection is well-documented in humans for up to 25 years with detectable viremia and anti-FV antibody response. Despite characteristic cytopathicity in vitro, FV have not been associated |
| 263 | Novel Envelope Structure Design Using Variable Loop and Beta-Sheet Modifications Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 263 Hartog K, Srivastava I, Kan E, Sharma V, Martin E, Donnelly J, Ulmer J, Barnett S;;; Chiron Corp. BACKGROUND: Vaccination with immunogens encoding the HIV envelope (Env) glycoprotein (primary-like SF162 virus) containing a partial deletion of the second hypervariable region resulted in higher neutralizing titers for the homologous virus as well as for several heterologous primary HIV type 1(HIV-1) isolates in rabbi |
| 264 | Design and Evaluation of Envelope Immunogens from Primary Subtype C HIV-1 Isolates Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 264 Lian Y, Srivastava I, Megede J, Sun Y, Kan E, Hilt S, Ulmer JB, Donnelly JJ, Engelbrecht S, Rensburg E, Barnett SW;;; Chiron Corp., Emeryville, CA, USA and 2Univ. of Stellenbosch, Tygerberg, South Africa BACKGROUND: A major challenge of HIV vaccine development is the diversity of HIV viruses. Our goals are to determine which Env structures will most efficiently present important neutralizing epitopes, and to achieve high-level expression of the env genes for gene delivery vaccine applications and for env protein produc |
| 265 | Developing HIV-1 Vaccine Using Human Parainfluenza Virus Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 265 Han D, Kim Y, Skiadopoulos M, Riggs J, Murphy B, Cho M;;; Case Western Reserve Univ., Cleveland, OH, USA and 2NIH, DHHS, Bethesda, MD, USA BACKGROUND: Despite recent successes in developing vaccine candidates that can control infection of highly pathogenic SHIV in macaques, more effective vaccines are likely needed to protect humans against HIV-1. Induction of a potent mucosal immunity against multiple HIV-1 gene products might allow for a faster immune r |
| 266 | Development of a DNA Vaccine Designed to Induce Cytotoxic T Lymphocyte Responses to Multiple Conserved Epitopes in HIV-1 Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 266 Livingston B, McKinney D, Anders M, MaWhinney S, Forster J, Newman M, Wilson C;;; Epimmune, San Diego, CA, USA and 2Univ. of Colorado Hlth. Sci. Ctr., Denver, USA BACKGROUND: There is evidence that cellular immune responses, specifically those mediated by CD8+ cytotoxic T-lymphocytes (CTL), can contribute to the control of HIV-1 replication. Although disease progression occurs in the presence of HIV-1 specific immune responses, CTL responses that are weak, narrowly-directed, or |
| 267 | Relative Efficacy of SHIV 89.6 Live Virus and DNA Provirus Vaccines Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 267 Busch M, Abel K, Fritts L, Lu D, Lifson JD, Miller Cl;;; California Natl. Primate Res. Ctr., Davis, USA BACKGROUND: Previously, we have shown that rhesus macaques infected with SHIV 89.6 are protected from intra-vaginal (IVAG) challenge with pathogenic SIVmac239. Since inoculation of animals with full-length proviral plasmids leads to systemic infection we hypothesized that inoculation of rhesus macaques with a plasmid c |
| 268 | Improved Presentations of Envelope Immunogens Derived From Subtypes B and C HIV-1 Provide Increased Breadth of Neutralizing Antibody Responses Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 268 Barnett SW, Srivastava I, Stamatatos L, Lian Y, Kan E, Sun Y, Montefiori D, Robert-Guroff M, Engelbrecht S, Rensburg E, Ulmer J, Donnelly J;;; Chiron Corp., Emeryville, CA, USA BACKGROUND: The most daunting challenge of present efforts to design an effective HIV-1 vaccine is to identify a structure and regimen for delivery of the envelope antigen for the efficient induction of broadly reactive neutralizing antibody responses against the diversity of transmitted strains. METHODS: Toward this e |
| 269 | Expression and Immunogenicity of Novel HIV-1 Subtype C Vaccine Candidates Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 269 Megede J, Otten G, Doe B, Liu H, Scriba T, Rensburg E, Ulmer J, Donnelly J, Barnett S;;; Chiron Corp., Emeryville, CA, USA and 2Univ. of Stellenbosch, Tygerberg, South Africa BACKGROUND: HIV-1 subtype C is the world s most predominant clade. Control of the ongoing HIV-1 epidemic will require novel vaccine approaches to induce potent, broad, and durable immune responses. Here we present the pre-clinical evaluation of subtype C vaccine candidates. METHODS: We previously performed studies of n |
| 270 | Neutralizing Antibody Responses Induced in Rhesus Macaques Using Different DNA Delivery Technologies as Prime and o-gp140deltaDV2 SF162 as Boost Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 270 Kan E, Otten G, Sun Y, Montefiore D, O'Hagan D, Singh M, Donnelly J, Ulmer J, Barnett S, Srivastava I;;; Chiron Corp., Emeryville, CA, USA and 2Duke Univ. Med. Ctr., Durham, NC, USA BACKGROUND: For the induction of humoral responses, focus has been on the induction of high avidity and primary isolate neutralizing antibodies. We have demonstrated that o-gp140deltaDV2 in prime-boost strategy is effective in inducing primary isolate neutralizing antibodies. In this study, we evaluated different DNA d |
| 271 | Neonatal Vaccination Provides Long-term Protection of Macaques against Oral SIV Exposure Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 271 Marthas M, Rompay KV, Earl P, Tartaglia J;;; Univ. of California, Davis, USA BACKGROUND: A neonatal vaccine to prevent HIV breast milk transmission is urgently needed. Ideally, a childhood HIV vaccine would also provide protection against later sexual exposure to HIV in adolescence. To test HIV vaccine candidates, we developed an infant rhesus macaque model to better mimic repeated oral HIV exp |
| 272 | Effect of SIV Lipopeptide Vaccination on Survival of Macaques: Major Role of CTL Responses on Delaying Onset of AIDS Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 272 Coutsinos Z, Mortara L, Beauchet A, Villefroy P, Gras-Masse H, Venet A, Levy JP, Guillet JG, Bourgault-Villada I;;; Paris, France and 2Lille, France BACKGROUND: Cytotoxic T lymphocytes (CTL) play a key role in the control of HIV/SIV infection. We have focused on a lipopeptide vaccination strategy, which has been shown to induce strong CTL responses in both animals and humans, in order to deliver SIV antigens to rhesus macaques. The aim of this work was to evaluate |
| 273 | Env-CD4 Complexes Induce Neutralizing Antibodies Against Heterologous Primary HIV-1 Isolates Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 273 Srivastava I, Sharma V, Kan E, Vita C, Martin L, Sun Y, Deck R, Ulmer J, Barnett S;;; Chiron Corp., Emeryville, CA, USA and 2CEA, Scalay, France BACKGROUND: We evaluated alternative strategies to expose functional epitopes on the HIV envelope protein that may be the targets for inducing high avidity and primary isolate neutralizing responses. Viral entry into CD4+ T cells is mediated by receptors (CD4) and co-receptors (CCR5). First, the virus binds to CD4, res |
| 274 | Potential Correlation of Structural Characterization and Immune Responses of Novel HIV Envelope Glycoproteins Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 274 Sharma VA, Kan E, Sun Y, Barnett S, Ulmer J, Srivastava IK;;; Chiron Corp., Emeryville, CA, USA BACKGROUND: HIV-1 envelope glycoprotein (Env) is the primary target for inducing neutralizing antibodies. Env is presented on the virus particle in one conformation as a trimeric complex; a second conformation ensues upon binding to the first host receptor (CD4). Structural rearrangement exposes co-receptor binding sit |
| 275 | Purification, Characterization and Immunogenicity of a Soluble Trimeric Envelope Protein Containing a Partial Deletion of the V2 Loop Derived from TV1, an R5-Tropic Subtype C HIV-1 Isolate Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 275 Srivastava I, Kan E, Sharma V, Stamatatos L, Lian Y, Hilt S, Matsuoka K, Wininger M, Sun Y, Engelbrecht S, Ransberg E, Donnelly J, Ulmer J, Barnett S;;; Chiron Corp., Emeryville, CA, USA BACKGROUND: The envelope (Env) glycoprotein of human immunodeficiency virus type 1 (HIV-1) is the major target of neutralizing antibody responses. Monomeric HIV envelopes have been limited in their ability to induce neutralizing antibodies against primary HIV isolates. The most likely reason is that the antigenic struc |
| 276 | Allo-immunization with Mamu-A*01 and DRw201 Vaccine Failed to Protect Rhesus Macaque from Infection of SIVmac239 Derived from Mamu-A*01 and DRw201 Positive PBMC Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 276 Guan Y, Luscher M, Rakasz E, Watkins D, Rustam T, Khanna N, Candido M, Tartaglia J, Burton D, MacDonald K;;; Mount Sinai Hosp. and Univ. of Toronto, Toronto, Canada BACKGROUND: The molecules of the major histocompatibility complex (MHC) are prominent among cellular proteins incorporated in the virion of both HIV and SIV. Since MHC molecules are immunogenic and vary significantly between individuals, yet are not subject to rapid mutation, unlike viral proteins, MHC allo-immunizatio |
| 277 | Therapeutic Immunization of SIVmac239-infected Rhesus Macaques, Using Inactivated SIV Virions with Intact Functional Envelope Glycoproteins Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 277 Lifson J, Piatak M Jr, Bess J Jr, Yuan F, Schneider D, Cline A, Coalter V, Poore B, Raz E, Richman D, Van Nest G, Bischofberger N, Hoxie J, Pope M, Arthur L;;; SAIC-Frederick, Inc., MD, USA BACKGROUND: Aldrithiol-2 (AT-2) inactivates retroviral infectivity by selective covalent modification of Cys on internal viral proteins, while preserving the structure and function of viral envelope glycoproteins, in which Cys are disulfide bonded. Potential advantages of AT-2-inactivated virions as vaccine immunogens |
| 278 | in vitro and in vivo Biological Characteristics of Subtype C Consensus and Ancestral Envelope Immunogens Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 278 Li Y, Weaver EA, Decker JM, Zammit KP, Korber BT, Chen Y, Kothe DL, Gao F, Shaw GM, Hahn BH;;; Univ. of Alabama at Birmingham, USA BACKGROUND: Codon-optimized HIV-1 subtype C consensus and ancestral envelope genes have been previously shown to produce functional envelope proteins that are able to incorporate into virus particles and can be recognized by serum antibodies of HIV-1 subtype-C-infected individuals. Because these synthetic envelopes app |
| 279 | Assessment of AIDS Vaccination Success by Repeated Low-dose Challenges Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 279 Regoes RR, Staprans SI, Feinberg MB;;; Emory Univ., Atlanta, GA, USA BACKGROUND: HIV vaccine trials in animal models are usually conducted with very high challenge doses that result in infection with certainty. Vaccine studies using these high challenge doses, however, do not realistically reflect the low probability of HIV transmission in humans, and thus may rule out vaccines that cou |
| 280 | Viral and CD8+ T Cell Dynamics in Vaccination and SHIV Challenge Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 280 Davenport MP, Ribeiro RM, Perelson AS;;; Univ. of New South Wales, Sydney, Australia BACKGROUND: Various vaccination strategies have been shown to induce CD8+ T cell responses to S(H)IV in macaques. These vaccine-induced CD8+ T cell responses don t appear to mediate sterilizing immunity, but do reduce long-term viremia and mortality. Analysis of viral and immune kinetics can help us understand the mech |
| 281 | High Levels of beta-Chemokine Expression Are Associated With Uncontrolled SIV Replication in the Lymphoid Tissues of Rhesus Macaques Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 281 LaFranco-Scheuch L, Abel K, Makori N, Rothaeusler K, Miller CJ;;; California Natl. Primate Res. Ctr., Davis, USA BACKGROUND: We have previously shown that immunization with SHIV89.6 protects approximately 60% of rhesus macaques against intravaginal challenge with pathogenic SIVmac239. In addition to classic antiviral CD8+ cytotoxic T-lymphocytes (CTL), viral suppression by non-cytolytic CD8+ T cells has been described in HIV and |
| 282 | The Relationship between IFN-gamma-driven Inflammation, SIV-specific IFN-gamma T-cell Responses and Challenge Outcome in Lymphoid Tissues of SHIV89.6-Immunized Rhesus Macaques after Intravaginal Challenge with SIVmac239 Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 282 Abel K, La Franco-Scheuch L, Rourke T, Ma ZM, Silva V, Fallert B, Beckett L, Reinhart TA, Miller CJ;;; Ctr. for Comparative Med., California Natl. Primate Res. Ctr., Univ. of California, Davis, USA BACKGROUND: Interferon-gamma (IFN-gamma) responses are used to assess HIV vaccine efficacy. Immunization with virulence-attenuated SHIV89.6 can protect rhesus macaques against intravaginal challenge with pathogenic SIVmac239. As IFN-gamma is a key mediator of antiviral defenses, but also a mediator of inflammation, and |
| 283 | Joint Assessment of HIV Vaccine Effects on Preventing Infection and Delaying Disease in the First Phase 3 Trial of AIDSVAX B/B Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 283 Gilbert PB, Cai T, Self SG, Gurwith M, Francis D;;; Fred Hutchinson Cancer Res. Ctr., Seattle, WA, USA BACKGROUND: In phase 3 preventive HIV vaccine trials, it is important to assess both vaccine efficacy to prevent infection (VEs) and disease progression (VEp) in subjects who become infected. Because vaccine effects on infection and post-infection endpoints are related, analytic methods are needed that evaluate VEs and |
| 284 | Assessment of HIV Vaccine Effects on Viral Load in the First Phase 3 Trial of AIDSVAX B/B Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 284 Shepherd B, Gilbert P, Gurwith M, Francis D;;; Univ. of Washington, Seattle, USA BACKGROUND: An imperfect vaccine could be useful if it prevents infection for some recipients and/or reduces morbidity and mortality among individuals who would be infected whether or not they received the vaccine. In a placebo-controlled phase 2 HIV vaccine trial, it is of interest to investigate the vaccine s impact |
| 285 | HIV Immune and Virological Responses following the Administration of IL-2 either alone or combined to ALVAC-HIV 1433 and HIV Lipopeptides in Patients Treated Early with HAART during Primary Infection: the ANRS 095 Randomized Study Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 285 Goujard C, Marcellin F, Chavez H, Meiffredy V, Rouzioux C, Venet A, Levy Y, Taoufik Y, Truchis P, Morlat P, Elhabib R, Mazarin V, Delfraissy JF, Aboulker JP ANRS 095 Study Group;;; Hosp. Bicetre, Le Kremlin-Bicetre, France BACKGROUND: HIV-specific immune responses are preserved in patients treated early during primary infection (PI). We evaluated whether the addition to HAART of IL-2 alone or combined with an immunization procedure might enhance HIV immune responses and improve viral control after HAART discontinuation. METHODS: We p |
| 286 | Evaluation of T-cell Immunogenicity of a Vaccination Strategy Combining ALVAC-HIV and HIV Lipopeptides Followed by SC IL-2 in Chronically HIV-infected Patients. Results of the ANRS093 Randomized Study Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 286 Levy Y, Gahery-Segard H, Durier C, Lascaux AS, Meiffredy V, Cassuto A, Goujard C, Rouzioux C, Habib RE, Beumont M, Guillet JG, Delfraissy JF, Aboulker JP ANRS 093 Study Group9;;; Hosp. Henri Mondor, Creteil, France BACKGROUND: Results from the ANRS093 study showed that the combination of ALVAC-HIV1433 / Lipo-6T vaccines and SC-IL2 induced sustained and polyepitopic specific proliferative CD4 responses and lowered the viral set point in patients for at least 3 months after stopping HAART. Specific T-cell responses were assessed. |
| 287 | CpG 7909 Administered with Hepatitis B Vaccine to HIV-infected Individuals Induces Helper Cell Responses to Hepatitis B Surface Antigen, but Not HIV Antigen Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 287 Angel JB, Cooper CL, Clinch J, Young CD, Chenier A, Parato KG, Lautru M, Davis H, Cameron DW;;; Ottawa Hlth. Res. Inst., Ontario, Canada BACKGROUND: Lack of adequate adjuvancy is a possible explanation for lack of vaccine immunogenecity. Immunostimulatory CpG are potent vaccine adjuvants (including for hepatitis B vaccine) and may be an important component of the development of an effective HIV vaccine. METHODS: We conducted a double-blind, placebo- |
| 288 | Timing and Factors Associated with Antiretroviral Use among Participants Who Became HIV Infected in a Phase 3 HIV Vaccine Trial Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 288 Buchbinder S, Wheeler SL, Vittinghoff E, Mayer KH, Celum C, Novak R, McKirnan D, Para MF, Gurwith M, Longhi M, Ackers M;;; San Francisco Dept. of Publ. Hlth. AIDS Office, CA, USA BACKGROUND: Future HIV vaccines may work primarily through modification of post-infection disease course. These efficacy trial endpoints will include time to surrogate markers of disease progression, such as initiation of antiretroviral therapy (ART) or low CD4+ count. Data from the first HIV vaccine efficacy trial, VA |
| 289 | Long-term Follow-up of Human Immunodeficiency Virus Seropositivity among Uninfected HIV Vaccine Recipients in France Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 289 Silbermann B, Launay O, Desaint C, Poncelet H, Souteyrand Y, Hesmati F, Pialoux G, Salmon-Ceron D;;; Cochin Hosp., Paris, France BACKGROUND: Immunization with HIV preventive vaccine constructs elicit antibodies detected by standard serologic tests. The objective of this study was to determine the frequency and the durability of vaccine-induced HIV antibodies among uninfected HIV vaccine trial participants. METHODS: Among the 76 vaccine participa |
| 290 | HIV-1 Acute Infection Env Glycomutants Designed from 3D-Model: Effects on Processing, Antigenicity and Neutralization Sensitivity Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 290 Reynard F, Verrier B, Bedin F;;; UMR2142 CNRS/bioMerieux, Lyon, France BACKGROUND: Vaccination trials carried out with Env protein have never succeeded mainly because the native Env complex has evolved to limit its overall immunogenicity by variable loops and extensive glycosylation. Only a few studies dealing with glycosylation sites have taken into account available 3-dimensional data i |
| 291 | Molecular Characterization of env genes From Primary HIV-2 Strains Unable to Use CCR5 or CXCR4 Co-receptors Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 291 Santos-Costa Q, Collman RG, Moniz-Pereira J, Azevedo-Pereira JM Univ. of Lisbon, Faculty of Pharmacy, Ctr. of Molecular Pathogenesis, Portugal and 2Univ. of Pennsylvania Sch. of Med., Philadelphia, USA BACKGROUND: HIV-2 infection is in general characterized by a slower disease progression and lower transmission rates. The reasons underlying these features are still basically unknown and the importance of HIV-2 as a model for understand pathogenicity of HIV infection has been in some cases underestimated. We have rece |
| 292 | Functional Analysis of the HIV-1 Envelope Bridging Sheet Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 292 Biscone M, Reeves J, Baribaud F, Baik S, Doms R;;; Univ. of Pennsylvania, Philadelphia, USA BACKGROUND: A series of four antiparallel beta-sheets linking the inner and outer domains of the gp120 subunit of HIV-1 envelope (Env) form a highly conserved structure among HIV-1 viral strains called the bridging sheet. This region is thought to face the cell surface following Env engagement by CD4, providing a struc |
| 293 | Characterization of HIV-1 Envelope Glycoproteins lacking Palmitoylated Cysteines in the gp41 Cytoplasmic Domain: Influence on Cell Surface Expression, Incorporation onto Virions and Infectivity Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 293 Bhattacharya J, Peters P, Clapham P;;; BACKGROUND: The gp41 cytoplasmic domain of HIV-1 envelope (env) contains conserved cysteines (C764/C837), which are palmitoylated. Palmitoylated cysteines were reported to target envs to lipid rafts for assembly onto budding virions. However, several cloned HIV-1 env lack gp41 cytoplasmic cysteines, yet are fully funct |
| 294 | C-terminal Truncations of the HIV-1 gp41 Define a Minimal Membrane Anchor and Toplogical Model for the Membrane-Spanning Domain Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 294 Yue L, Brown N, Hunter E;;; Univ. of Alabama at Birmingham, USA BACKGROUND: Previous studies have implicated a region of 23 amino acids in gp41 that is flanked by an N-terminal lysine (residue 681 in Env) and a C-terminal arginine (residue 705) as the membrane anchor of this protein. However, this model places a basic residue (arginine 694) in the center of the lipid bilayer -- an |
| 295 | Formation of a Salt Bridge between the N- and C-terminal Heptad Repeats of HIV-1 gp41 Is Critical for Stabilization of 6-Helix Bundle and Virus Fusion Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 295 He Y, Liu S, Debnath AK, Jiang S;;; BACKGROUND: Binding of HIV-1 to CD4 and a receptor results in a series of conformational rearrangements in gp41. Its N- and C-terminal heptad repeats form a stable 6-helical bundle, which represents a fusion-active gp41 core. Crystallographic analysis suggest that a negatively charged residue, Asp632, in the C-terminal |
| 296 | The Membrane Proximal Tyrosine-Based Sorting Signal of HIV-1 gp41 Is Required for Optimal Viral Infectivity and Viral Entry Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 296 Day J, Guatelli J;;; Univ. of California, San Diego, USA and 2San Diego VA Healthcare System BACKGROUND: The membrane proximal tyrosine-based sorting motif in the cytoplasmic domain of the HIV-1 envelope glycoprotein (Env) is important for endocytosis of Env from the plasma membrane, basolateral targeting of viral budding in polarized epithelial cells, and polarized budding from a localized region of the lymph |
| 297 | Dually Inducible Cell Lines to Study the Quantitative CD4 and Co-receptor Dependence of HIV Envelopes Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 297 Baik S, Lee B;;; Univ. of California, Los Angeles-MIMG, USA BACKGROUND: The affinity of gp120 to CD4 has been demonstrated to bemuch greater than its affinity to coreceptor. And gp120s from variousvirus strains bind with different affinities to their cognatecoreceptor, CCR5 or CXCR4. By being able to independently modulate (CD4and coreceptor) densities on the cell surface over |
| 298 | The HIV-1 Envelope Proteins of Patients Isolates with Naturally Occurring Cytoplasmic Tail Deletions Exhibit Altered Membrane Fusion and Infectivity Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 298 Huang W, Toma J, Whitcomb J, Fransen S, Wrin T, Penuel E, Petropoulos C;;; ViroLogic Inc., South San Francisco, CA, USA BACKGROUND: The transmembrane glycoprotein (gp41) of HIV-1 envelope has a long (~150 amino acids) and highly conserved cytoplasmic domain. Previous studies have suggested roles for this domain in envelope incorporation, virus infectivity, and replication, however the precise functions of this region are not clearly def |
| 299 | HIV Envelope-induced Syncytium Formation Is Dependent on Actin Cytoskeletal Reorganization and Co-receptor-mediated Activation of Rac-1 GTPase Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 299 Pontow S, Heyden NV, Ratner L;;; Washington Univ. Sch. of Med., St. Louis, MO, USA BACKGROUND: The membrane fusion events that initiate HIV-1 infection and promote cytopathic syncytium formation in infected cells commence with the binding of HIV envelope glycoprotein (Env) to CD4 and an appropriate co-receptor. The currently accepted model of syncytium formation suggests that HIV-induced cell fusion |
| 300 | Env Content in Virions as an Important Determinant of Relative Sensitivity to Antibody-mediated Neutralization Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 300 Yuste E, Desrosiers R;;; New England Primate Res. Ctr., Harvard Med. Sch., Southborough, MA, USA BACKGROUND: Env content in virions of SIV and HIV and its influence on different biological properties is poorly understood. Initial reports suggested about 72 spikes per HIV virion, although recent reports indicate this number may be considerably lower. In lentiviruses, envelope (Env) glycoproteins with long cytoplasm |
| 301 | Use of Fc-gp120 Adhesins To Characterize Receptor Interactions Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 301 Parseval A, Binley J, Ngo S, Burton D, Elder J;;; Scripps Res. Inst., La Jolla, CA, USA BACKGROUND: We have developed a panel of HIV-1 Fc-SU adhesins to characterize the interaction gp120 with its receptor, co-receptor, and attachment co-factors such as DC-SIGN. METHODS: Wild type, as well as V3-deleted, V1V2-deleted, and V1V2V3-deleted mutants of gp120 from the JR-CSF strain of HIV-1 were sub-cloned down |
| 302 | Semen-specific Genetic Characteristics of HIV-1 env Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 302 Pillai S, Good B, Wong J, Strain M, Richman D, Smith D;;; Univ. of California, San Diego, USA and 2VA San Diego Healthcare System, La Jolla, CA, USA BACKGROUND: The design of an effective HIV-1 vaccine will depend largely on characterizing and selectively combating virus from genital secretions. Ample evidence indicates that tissues in the male genital tract (MGT) support HIV-1 replication. This virus may be genetically distinct, due to tissue-specific cellular cha |
| 303 | Identification of High-mass Oligomers of DC-SIGN on Monocyte-Derived Dendritic Cells and Preferential Recognition by Mannan and HIV-gp120 Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 303 Bernhard OK, Wilkinson J, Sheil MM, Cunningham AL;;; Ctr. for Virus Res., Westmead, Australia and 2Univ. of Wollongong, Australia BACKGROUND: DC-SIGN is a 44-kDa type II transmembrane protein expressed by dendritic cells (DC), which binds to high mannose glycoproteins promoting their endocytosis and degradation. It also mediates attachment and endocytosis of HIV to DC through recognition of the carbohydrate structures on the envelope protein gp12 |
| 304 | Identification of Monoclonal Antibodies that Define HIV-1 Immunotypes Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 304 Nadas A, Zhong P, Burda S, Zekeng L, Gorny M, Nyambi P;;; New York Univ. Sch. of Med., NY, USA and 2Lab. de Sante Hygiene Mobile, Yaounde, Cameroon BACKGROUND: Studies that examine the genetic and antigenic properties of HIV-1 isolates reveal that genetic diversity does not parallel antigenic diversity and that HIV-1 strains from different geographic regions can be grouped into a small number of immunologically defined groups (immunotypes). METHODS: HIV-1 subtype |
| 305 | Inhibition of HIV-1 Entry: Broadly HIV-1 Neutralizing Human Monoclonal Antibodies and Their Derivatives Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 305 Zhang MY, Dimitrov DS;;; HIVCB, LECB, NCI-Frederick, NIH, DHHS, Frederick, MD, USA BACKGROUND: The identification of new broadly cross-reactive HIV human monoclonal antibodies (nhmAbs) and characterization of their conserved epitopes is important for the development of HIV inhibitors. Fab X5 was found to inhibit primary HIV-1 isolates from different clades. ScFv m6 and m9 which were derived from Fab |
| 306 | Rapid Screening of Subtypes B and C Neutralizing Antibody Responses Against PBMC Grown HIV-1 Isolates in an Engineered CEM Cell Line Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 306 Sun Y, Sharma V, Srivastava I, Kan E, Landau N, Barnett S;;; Chiron Corp., Emeryville, CA, USA and 2Salk Inst., San Diego, CA, USA BACKGROUND: PBMC based assays are usually time consuming and costly. The purpose is to establish a high throughput neutralization assay using an engineered CEM cell line that can detect neutralizing antibody activity and also establish a correlation between the antibody binding profile and neutralizing activity against |
| 307 | HIV-1 Envelope Determinants of CXCR4-mediated Infection of Macrophages: Utilization of CXCR4 by HIV-1 Is Cell-type-specific Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 307 Tuttle D, Ghaffari G, Jeffers L, Briggs D, Sleasman J, Goodenow M;;; Univ. of Florida, Gainesville, USA and 2Univ. of South Florida and All Children's Hosp., St. Petersburg, USA BACKGROUND: CXCR4 (X4) strains of HIV-1 are associated with advanced disease in individuals infected by subtype B viruses. Although all X4 strains infect PBMC and T-cell lines, D-X4 strains infect monocyte-derived macrophages (MDM), while T-X4 strains do not. In vivo, T-X4 strains evolve from D-X4 strains, indicating a |
| 308 | Envelope-mediated Membrane Fusion of Patient HIV-1 Isolates Varies with Co-receptor Usage Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 308 Huang W, Fransen S, Toma J, Petropoulos CJ, Whitcomb JM;;; ViroLogic Inc., South San Francisco, CA, USA BACKGROUND: HIV-1 co-receptor tropism has been associated with disease stage. CCR5 (R5) isolates predominate early in asymptomatic infection, while CXCR4 (X4) and dual (X4/R5) tropic isolates often emerge at later stages. However, many late-stage patients progress to AIDS and death in the absence of X4 variants. This s |
| 309 | Characterization of Membrane Dynamics and Virion Fusion Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 309 Henderson H, Hope TJ;;; Univ. of Illinois at Chicago, USA BACKGROUND: HIV infection is a multistep process that occurs by membrane fusion of virus and target cells. Through interactions between gp120 and coreceptors, a 6 helix bundle is formed leading on the formation of fusion pores and release of the viral genome into target cells. Although many of the factors required for |
| 310 | Effect of Envelope Co-receptor Affinity on Fusion, Infection, and Entry Inhibitor Sensitivity Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 310 Reeves J, Miamidian J, Biscone M, Lee FH, Ahmad N, Pierson T, Doms R;;; Univ. of Pennsylvania, Philadelphia, USA BACKGROUND: An increasingly large number of novel antiviral agents that prevent entry of HIV into cells are in preclinical and clinical development. The envelope (Env) protein of HIV is the major viral determinant that impacts sensitivity of virus to these compounds. To understand how changes in Env can impact entry in |
| 311 | Identification of Small Molecule HIV-1 Fusion Inhibitors Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 311 Salzwedel K, Crisafi K, Jackson T, Castillo A, Kilgore N, Reddick M, Allaway G, Wild C;;; Panacos Pharm., Gaithersburg, MD, USA BACKGROUND: Fusion inhibitors are a promising new class of HIV therapeutics that act by blocking conformational changes in the HIV envelope glycoprotein (Env) that drive fusion of the viral and cellular membranes during virus entry. Proof of concept for this therapeutic approach is provided by the recently approved inh |
| 312 | HIV-1 Infection Is Associated with Altered Phenotype and Function of DC-SIGN+ Dendritic Cells in the Human Gut Mucosa Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 312 Gurney K, Elliott J, Nassanian H, Song C, Gowan IM, Anton P, Lee B;;; Univ. of California, Los Angeles, Sch. of Med., USA BACKGROUND: DC-SIGN is expressed on dendritic cells (DC) in the gut mucosa. We undertook a study to phenotype and examine the function of DC-SIGN+ DC in HIV+ and HIV- individuals. METHODS: Recotsigmoid biopsies from HIV+ and HIV- patients and monocyte derived dendritic cells (MDDC) cultured with various cytokine combin |
| 313 | HIV Recognition of both CCR5 and Syndecan Depends on 2 Highly Conserved Arginines in the V3 Loop of Gp120 Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 313 Bobardt M, Parseval A, Elder J, Lee TH, David G, Gallay P;;; Scripps Res. Inst., La Jolla, CA, USA BACKGROUND: Although the entry receptors CD4 and CXCR4/CCR5 are absolutely required for HIV replication, a growing body of evidence suggests that other receptors affect HIV pathogenesis, the attachment receptors. We previously examined the capacity of a specific class of attachment receptors, the syndecans, to influenc |
| 314 | Delineating DC-SIGN Binding to gp120, ICAM2, and ICAM3 Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 314 Su S, Hong P, Lee B;;; Univ. of California, Los Angeles, USA BACKGROUND: DC-SIGN, binds to HIV gp120 and mediates the binding and transfer of HIV from dendritic cells (DC) to permissive T-cells. DC-SIGN also binds to ICAM2 and ICAM3, endogenous ligands that mediate DC extravasation and T-cell/DC clustering, respectively. METHODS: gp120Fc, ICAM2Fc, ICAM3Fc, and the soluble extrac |
| 315 | Cellular and Molecular Requirements of DC-SIGN-mediated HIV-1 Transmission Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 315 KewalRamani VN;;; NCI, NIH, DHHS, Frederick, MD, USA BACKGROUND: Monocyte-derived dendritic cell (MDDC) can efficiently transmit HIV-1 to target cells by concentrating captured virus at sites of cell-cell contact. DC-SIGN is a key mediator of MDDC transmission of HIV-1 to CD4+ T cells. DC-SIGN-mediated HIV-1 transmission (DMHT) can be reconstructed with transformed cell |
| 316 | Fusion Differences between R5 and X4 HIV-1 in Dendritic Cells: Implications for Selective Transmission of R5 Strains Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 316 Cavrois M, Neidleman JA, Callebaut C, Kreisberg JF, Fenard D, Greene WC;;; Gladstone Inst. of Virology and Immunology, Univ. of California, San Francisco, USA BACKGROUND: Dendritic cells (DC) are key players in the natural history of HIV infection. Immature DC, such as langerhans cells, are one of the earliest targets for HIV infection in the genital or rectal epithelia. Due to their capacity to traffic from peripheral sites to lymph nodes, immature DC are thought to play a |
| 317 | R5 HIV-1 Strains Replicate More Efficiently in Primary CD4+ T Cell Cultures than X4 HIV-1 Strains Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 317 Schweighardt B, Meiklejohn DA, Grace EJ III, Nixon DF;;; Gladstone Inst. of Virology and Immunology, Univ. of California, San Francisco, USA BACKGROUND: R5 HIV-1 strains often represent the dominant viral population detected during the early stages of clinical HIV-1 infection. The more pathogenic X4 strains are typically detected in the later stages of infection, and are associated with rapid CD4+ T-cell loss. We present evidence that R5 strains replicate m |
| 318 | Preferential Utilization of CXCR4 in Primary Lymphocytes but not in Primary Macrophages by R5X4 Strains: Implication for Viral Tropism, Evolution and Pathogenesis Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 318 Yi Y, Laddy D, Collman R;;; Univ. of Pennsylvania, Philadelphia, USA BACKGROUND: CCR5 & CXCR4 are the main co-receptors used by HIV-1 in primary blood lymphocytes (PBL) and monocyte-derived macrophages (MDM). R5 isolates predominate early, and CXCR4 use often emerges later in association with disease progression. Most late-stage CXCR4-using isolates demonstrate an R5X4 phenotype whe |
| 319 | Virus Transmission by Dendritic Cells in a Non-pathogenic Model of SIV Infection Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 319 Ploquin MJ, Diop OM, Sol-Foulon N, Mortara L, Faye A, Amara A, Schwartz O, Barre-Sinoussi F, Muller-Trutwin MC UBR, Inst. Pasteur, Paris, France BACKGROUND: African green monkeys infected by SIVagm do not develop AIDS. This lack of disease is associated with low RNA and DNA viral loads in lymph nodes despite a high plasma viremia. In order to investigate the role of dendritic cells in SIVagm dissemination to lymph nodes, we analyzed here the capacity of African |
| 320 | Attachment Levels of HIV Differ between PBMC Donors in a CD4-independent Manner Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 320 Anzinger J, Spear G, Mezo I, Saifuddin M;;; Rush Univ., Chicago, IL, USA and 2CONRAD Prgm., Arlington, VA, USA BACKGROUND: Human Immunodeficiency Virus (HIV) attachment to cell surface molecules is essential for viral entry into cells expressing CD4 and coreceptor (CXCR4/CCR5). In this study we examined HIV primary isolate attachment to peripheral blood mononuclear cells (PBMC) of different donors. METHODS: HIV isolates were pr |
| 321 | The N-Terminal Domain of APJ, a CNS-based Co-receptor for HIV-1, Is Essential for its Novel Receptor Function and Co-receptor Activity Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 321 Zhou N, Zhang X, Fan X, Argyris E, Fang J, Acheampong E, DuBois G, Pomerantz R;;; Thomas Jefferson Univ., Philadelphia, PA, USA BACKGROUND: The human receptor APJ, a member of the G protein-coupled seven-transmembrane receptor family, has been shown to play an important role in mediating neuroendocrine effects in the human CNS, and also to serves as a co-receptor for the entry of human immunodeficiency virus type I (HIV-1) and simian immunodefi |
| 322 | Host Range Extension of Avian Leukosis Virus Following Extensive Passage in Chick Embryo Fibroblasts Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 322 Negusse D, Drew L, Coffin J;;; Tufts Univ., Boston, MA, USA and 2Univ. of Bath, UK BACKGROUND: Retroviruses, due to the low fidelity of the replication cycle can accumulate mutations that eventually alter their phenotype, resulting in strains with different growth properties such as increased cytopathic effect and altered host range or tropism. Viruses with expanded host range may have a selective ad |
| 323 | Effect of Sera from HIV-1-infected Individuals on HIV Envelope-dependent Cell-cell Fusion Is Related to the CD4+ Cell Counts, Viral Load, and Clinical Status Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 323 Huerta L, Gomez-Icazbalceta G, Soto-Ramirez L, Viveros-Rogel M, Rodriguez-Diaz R, Fuentes-Romero L, Lamoyi E, Larralde C;;; Inst. de Investigaciones Biomedicas, UNAM, Mexico City, MEXICO and 2Natl. Inst. of Med. Sci. and Nutrition, Mexico City, Mexico BACKGROUND: Isolation of syncytium inducing human immunodeficiency virus type 1 (HIV-1) strains from the circulation of infected persons is associated with an increased rate of T CD4+ lymphocyte depletion and progression to AIDS. Since fusion of T CD4+ cells by HIV-1 envelope proteins is a mechanism of virus spread and |
| 324 | Role of HIV-1 Matrix Phosphorylation in an Early Post-entry Step of Virus Replication Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 324 Kaushik R, Ratner L;;; Washington Univ. Sch. of Med., St Louis, MO, USA BACKGROUND: The matrix domain (MA) is important for targeting HIV-1 Gag assembly to the plasma membrane, envelope incorporation into virions, pre-integration complex import into the nucleus, and nuclear export of viral RNA. Myristoylation and phosphorylation are key regulatory events for MA function. Previous studies h |
| 325 | The MA Protein as a Regulator of HIV-1 Core Stability Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 325 Davis MR, Aiken C;;; Vanderbilt Univ. Sch. of Med., Nashville, TN, USA BACKGROUND: Following fusion of HIV-1 with a target cell, the internal viral core is released into the cytoplasm. MA co-purifies with viral cores isolated from detergent-treated virions and remains associated with reverse transcription complexes isolated from infected cells. Several MA mutants have been identified that |
| 326 | The Dimer Interface of the HIV Protease Is a Key Specificity Determinant of GagPol Processing Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 326 Kaplan AH, Everitt L, Choudhury S, Pettit SC;;; Univ. of North Carolina at Chapel Hill, USA BACKGROUND: The protease of HIV is translated as part of the GagPol polyprotein precursor and is both necessary and sufficient for complete precursor processing. As is the case for all retroviruses, the HIV protease is only functional as a dimer. The consequence of this arrangement is that 2 GagPol molecules must dimer |
| 327 | Structural Variability of the Initiation Complex of HIV-1 Reverse Transcription Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 327 Goldschmidt V, Paillart CJ, Rigourd M, Beyer C, Aubertin AM, Ehresmann B, Ehresmann C, Marquet R;;; CNRS, Strasbourg, France and 2INSERM, Strasbourg, France BACKGROUND: HIV-1 reverse transcription is initiated from the tRNA3Lys primer annealed to the primer binding site (PBS). In vitro experiments on the HIV-1 Mal isolate revealed that an interaction between the anticodon loop of the primer tRNA and a loop located 5 to the PBS is crucial for initiation of reverse transcrip |
| 328 | The Infectivity Enhancement of HIV-1 Nef Involves the Actin Cytoskeleton Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 328 Campbell EM, Hope TJ;;; Univ. of Illinois at Chicago, USA BACKGROUND: The HIV accessory protein Nef is known to increase the infectivity of virions. It is known that pseudotyping HIV virions with pH-dependent envelope proteins complements the infectivity of virions lacking a functional Nef protein (DNef) to near wild type levels. We report that depolymerization of the actin c |
| 329 | Evidence that Cell Cycle Arrest in G2 Can Promote the Early Steps of HIV Infection Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 329 Groschel B, Bushman FD;;; Salk Inst. for Biological Studies, La Jolla, CA, USA BACKGROUND: The antitumor agent etoposide induces DNA damage by inhibiting religation of cleaved topoisomerase II DNA complexes, thereby stabilizing DNA double strand. The etoposide-induced DNA damage results in cell cycle arrest in the G2 phase of the cell cycle. The HIV protein Vpr has been proposed to arrest cells i |
| 330 | The Carboxyl Terminus of HIV-1 Integrase Facilitates Viral Nuclear Import Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 330 Cunningham T, Kaufman D, Topper M, Muesing M, Luo Y Aaron Diamond AIDS Res. Ctr., Rockefeller Univ., New York, NY, USA BACKGROUND: After fusion and entry, the HIV-1 must navigate its genome through the cytosol and into the nucleus of its target cells, where integration into the host s chromosomal DNA subsequently occurs. The precise mechanism of nuclear entry, as well as the identity of the cellular factors and viral determinants that |
| 331 | Kinetics of the 3' Processing Reaction of HIV-1 Integrase as Determined by Fluorescence Cross Correlation Spectroscopy Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 331 Vercammen J, Witvrouw M, Clercq ED, Debyser Z, Engelborghs Y Lab. for Biomolecular Dynamics, Katholieke Univ. Leuven, Belgium and 2Rega Inst. for Med. Res., Katholieke Univ. Leuven, Belgium and The European TRIoH Consortium BACKGROUND: We have previously determined the association constant of fluorescent oligonucleotides to HIV-1 integrase using Fluorescence Correlation Spectroscopy (Vercammen et al., J. Biol. Chem., 277, 38045-38052 (2002)). METHODS: We have now developed a method to investigate the kinetic reactions of HIV-1 integrase w |
| 332 | The Relationship Between Retroviral Integration and Host Cell Transcription Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 332 Maxfield L, Bell N, Fraize C, Coffin J;;; Tufts Univ., Boston, MA, USA BACKGROUND: Our goal is to define properties of host cell DNA that influence sites of retroviral integration. Traditionally, integration was thought to prefer transcriptionally active over inactive DNA; however, previous data from our lab suggested that there are fewer integration events into a DNA template undergoing |
| 333 | Targeting of Lentiviral and Retroviral Integration Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 333 Mitchell R, Beitzel B, Schroder A, Shinn P, Chen H, Berry C, Ecker J, Bushman F;;; Salk Inst. for Biological Studies, La Jolla, CA, USA BACKGROUND: Integration of the retroviral cDNA into the host cell genome is essential for retroviral replication. This feature has made retroviruses attractive gene therapy vectors. However the danger of these vectors causing insertional mutagenesis became reality in a recent gene therapy trial, underscoring the import |
| 334 | Mutation of alpha-Helix 6 of the HIV-1 IN Central Domain Causes Loss of DNA Synthesis and Disrupts the Quaternary Structure of Integrase Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 334 Padow M, Kappes J Univ. of Alabama at Birmingham, USA BACKGROUND: The retroviral integrase (IN) protein augments initiation of reverse transcription in infected cells. Chimeric HIV-1 virus containing the HIV-2 IN gene is severely impaired in DNA synthesis and infectivity. Continuous culture of the chimeric virus selected for 3 mutations in IN (Q96H, K127E, V204I) that sig |
| 335 | Integration Sites of HTLV-I Provirus in Adult T-cell Leukemia Cells Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 335 Doi K, Kodama EI, Satou Y, Yasunaga JI, Taniguchi Y, Matsuoka M;;; Inst. for Virus Res., Kyoto Univ., Japan BACKGROUND: In HIV-1, its provirus tends to be integrated in the transcriptional units, suggesting that chromatin accessibility influences the integration step. Another human retrovirus, human T-cell leukemia virus type I (HTLV-I) is the causative virus of adult T-cell leukemia (ATL). In HTLV-I, the free virion can not |
| 336 | Structure of the 5'-Untranslated Region of HIV-1 Genomic RNA in Infected Cells and in Viral Particles Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 336 Paillart CJ, Dettenhofer M, Yu XF, Ehresmann B, Ehresmann C, Marquet R;;; CNRS, Strasbourg, France and 2Johns Hopkins Sch. of Hygiene and Publ. Hlth., Baltimore, MD, USA BACKGROUND: The HIV-1 genome contains 2 homologous positive RNA strands stably associated through several contacts all along the RNA genome. The 5 -untranslated region (5 -UTR) is the most conserved part of the HIV-1 RNA genome, and contains extensive secondary and tertiary structures that regulate key steps in the vir |
| 337 | Communication between the Spatially Separate Active Site and Dimer Interface of KSHV Protease Revealed by Small Molecule Inhibition Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 337 Marnett A, Nomura A, Shimba N, Mahrus S, Montellano P, Craik C;;; Univ. of California, San Francisco, USA BACKGROUND: All human herpesviruses use a homologous virally encoded maturational protease for the formation of infectious virions. Protease activity is regulated by dimerization, with each active dimer containing two spatially separate active sites. Circumstantial evidence supporting a relationship between activity an |
| 337b | LEDGF/p75 Determines Cellular Trafficking of Diverse Lentiviral but not Murine Oncoretroviral Integrase Proteins and Is a Component of Functional Lentiviral Pre-integration Complexes Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 337b Poeschla E, Llano M, Vanegas M, Fregoso O, Saenz D, Chung S, Peretz M Mayo Clin. Coll. of Med., Rochester, MN, USA BACKGROUND: Trafficking of HIV-1 pre-integration complexes (PIC) into and within nuclei is poorly understood. Karyophilic properties of PIC components have therefore drawn much interest. The transcriptional co-activator LEDGF/p75 interacts with HIV-1 integrase and determines nuclear localization of GFP-HIV-1 integrase |
| 338 | Attenuated Membrane-binding of HIV-1 Gag Protein Caused by Mutations of the CA-NC Spacer Sequences Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 338 Guo X, Hu J, Roldan A, Wainberg MA, Liang C McGill AIDS Ctr., Montreal, Canada BACKGROUND: Lentiviral Gag protein contains a short spacer sequence that separates the capsid (CA) from the downstream nucleocapsid (NC) domain, which has been shown to play an important role in the assembly of HIV-1. However, the mechanisms underlying its role in virus particle production are still unclear. Recently, |
| 339 | The p2 Spacer Peptide in HIV-1 Gag Plays a Critical Role in Genome Packaging Specificity Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 339 Russell RS, Spira B, Liang C, Wainberg MA McGill AIDS Ctr., Montreal, Canada BACKGROUND: During the retroviral assembly process, the HIV-1 Gag structural protein specifically encapsidates two copies of full-length viral genomic RNA into the newly forming virion. We previously showed that HIV-1 mutant viruses containing deletions in the 5 untranslated region of the viral RNA genome (i.e. the dim |
| 340 | N-terminal Extended NC Shows Stronger Affinity for HIV Genomic RNA than NC Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 340 Roldan A, Russell RS, Spira B, Liang C, Wainberg MA McGill AIDS Ctr., Lady Davis Inst.-Jewish Gen. Hosp., Montreal, Canada BACKGROUND: HIV-1 Gag is synthesized in the cytoplasm of infected cells as a polyprotein composed of 3 major domains: Matrix, Capsid (CA), and Nucleocapsid (NC). We know that alone this precursor is able to produce virus-like particles (VLP) and specifically encapsidate HIV genomic RNA (gRNA). CA is known to drive the |
| 341 | Defects In HIV-1 Budding and Endosomal Sorting Induced by TSG101 Overexpression Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 341 Goila-Gaur R, Demirov DG, Ono A, Freed EO;;; HIV Drug Resistance Prgm., NCI, NIH, DHHS, Frederick, MD, USA BACKGROUND: Retrovirus budding is greatly stimulated by the presence in Gag of sequences known as late or L domains. The L domain of HIV-1 maps to a highly conserved Pro-Thr-Ala-Pro (PTAP) motif in p6-Gag. Recent studies from our lab and others indicate that HIV-1 budding requires the host protein TSG101, which plays a |
| 342 | Locations and Determinants of HTLV-1 Particle Release Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 342 Wang H, Mansky LM;;; The Ohio State Univ., Columbus, USA BACKGROUND: In retroviruses, the late (L) domain has been defined as a conserved motif in the Gag polyprotein precursor (PrGag) that when mutated leads to an abundance of virus particles that begin to pinch off from the plasma membrane of the cell but do not completely release from the cell surface. These domains have |
| 343 | Direct Evidence for Virion-associated Lipid Rafts in HIV and SIV in Vesicle-depleted Virion Preparations Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 343 Graham DR, Hildreth JE;;; Johns Hopkins Sch. of Med., Baltimore, MD, USA BACKGROUND: HIV-1 particles assemble and bud selectively through lipid rafts in the plasma membrane of cells. Although the composition of the virus is similar to lipid rafts, contaminating cellular vesicles that co-purify with virions hinder attempts to characterize virion membrane organization. We have developed a new |
| 344 | Actin Cytoskeleton Dynamics and Equine Anemia Infectious Virus Assembly and Budding Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 344 Chen C, Weisz OA, Jin J, Stolz DB, Watkins SC, Montelaro RC;;; Univ. of Pittsburgh Sch. of Med., PA, USA BACKGROUND: Retrovirus assembly and budding involves a highly concerted interaction of viral and cellular proteins. Previous studies demonstrate that retroviral Gag proteins interact with actin filaments, but the significance of these interactions remains elusive. METHODS: We used equine infectious anemia virus (EIAV) |
| 345 | Gag-Pol and Viral Genomic RNA Molecules Are Preferentially Packed in cis in Viable HIV-1 Particles Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 345 Aguiar RS, Pereira HS, Brindeiro R, Tanuri A;;; Federal Univ. of Rio de Janeiro, Brazil BACKGROUND: The gag and pol genes from HIV-1 are initially translated as polyproteins encoded by the same mRNA. The HIV-1 unspliced RNA is both the messenger RNA that produces gag and gag-pol and the genomic RNA that is packaged into the virion. In this way, the vRNA can be packed in cis - associated with the cognate g |
| 346 | Role of Gag-Gag Interaction in HIV-1 Assembly: Cytoplasmic Cooperative Multimerization of Gag Allows its Transport to Membrane Assembly Sites Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 346 Perez-Caballero D, Hatziioannou T, Bieniasz P;;; Aaron Diamond AIDS Res. Ctr., Rockefeller Univ., New York, NY, USA BACKGROUND: The retrovirus polyprotein Gag is the only viral protein required for formation, budding, and release of virus-like particles (VLP) from the plasma membrane. Some current models support the idea that single Gag molecules bind to and subsequently multimerize at the inner face of the plasma membrane. However |
| 347 | Mutational Analysis of the HIV-1 Rev Response Element in the Context of Virus Replication Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 347 Ward A, Rekosh D, Hammarskjold ML;;; Myles H. Thaler Ctr. for AIDS and Human Retrovirus Res., Univ. of Virginia, Charlottesville, USA BACKGROUND: HIV-1 utilizes alternative splicing to produce 15 proteins from a 9-kb genome, giving rise to unspliced, singly and multiply spliced RNAs. The unspliced and singly spliced RNAs contain introns and encode the viral structural proteins as well as the Vif, Vpr, and Vpu accessory proteins. Typically, cellular R |
| 348 | HIV-1 Nef Self-associates in the Membrane Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 348 Alexander M, Hammarskjold ML, Rekosh D;;; Univ. of Virginia, Charlottesville, USA BACKGROUND: Nef targeting to the membrane is mediated by myristoylation and is important for most of its activities. Nef is also known to interact with a variety of proteins. This study is aimed at identifying Nef protein complexes present in transfected cells. METHODS: 293T cells or SupT1 cells were transiently transf |
| 349 | Interferon-alpha Inhibits Human T cell Leukemia Virus Assembly by Preventing Gag Interaction with Rafts Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 349 Kaushik R, Feng X, Heyden NV, Ratner L;;; Washington Univ. Sch. of Med., St. Louis, MO, USA BACKGROUND: Interferon-g (IFN-g2a) has beneficial clinical effects on HTLV-1 infection, but its antiviral mechanism of action is unknown. METHODS: Antiviral effects of IFN-g2a were studied in 293T cells expressing HTLV-1 proviral DNA and in HTLV-1-infected cells (HOS/PL, MT2, HUT102). In 293T cells, an IC50 of 10 U/mL |
| 350 | HIV and the Actin Cytoskeleton: Passenger or Player in Virus Assembly? Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 350 Krogstad P, Geng Y, Ibarrondo F;;; David Geffen Sch. of Med., Univ. of California, Los Angeles, USA BACKGROUND: Numerous cellular proteins have now been implicated as participants in the assembly and release of infectious HIV virions from target cells. The HIV Gag protein appears to be targeted to lipid raft microdomains of the plasma membrane, where it interacts with spatially sequestered proteins. The presence of a |
| 351 | APOBEC3G: A Potent Viral DNA Mutator from the Host. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 351) Zhang H, Yang B, Pomerantz RJ, Chen K, Arunachalam SC, Zhang C, Gao L; Thomas Jefferson Univ., Philadelphia, PA, USA BACKGROUND: It has been demonstrated that many host factors are involved in the replication of human immunodeficiency virus type 1 (HIV-1). Recent development has indicated that a novel host factor, APOBEC3G (also named as CEM15), has potent antiviral activities. Its inhibitory effect can be effectively counteracted by |
| 352 | Species-specific Target Specificity of APOBEC3G. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 352) Kobayashi M, Takaori-Kondo A, Shindo K, Abudu A, Sasada A, Uchiyama T; Kyoto Univ. Sch. of Med., Japan BACKGROUND: APOBEC3G, also known as CEM15, is a broad antiretroviral host factor by deaminating dC to dU in the minus strand DNA of HIV-1, other lentiviruses, and murine leukemia virus, thereby creating G to A hypermutation in the plus strand DNA to inhibit the infectivity of these viruses. In this study, we examined t |
| 353 | A Single Amino Acid Change Controls the Ability of HIV-1 Vif to Discriminate Between Human and African Green Monkey APOBEC3G. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 353) Doehle B, Bogerd H, Wiegand H, Cullen B; Duke Univ., Durham, NC, USA and 2Howard Hughes Med. Inst. BACKGROUND: Human APOBEC3G (hAPOBEC3G) is specifically packaged into the virions of Vif- HIV-1 and then inhibits virus replication by massively editing the minus strand of the viral DNA during reverse transcription. While the anti-retroviral activity of hAPOBEC3G is overcome by HIV-1 Vif, African green monkey APOBEC3G |
| 354 | Biophysical and Structural Analysis of HIV-1 Vif and its Cellular Inhibitor APOBEC3G. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 354) Auclair J, Somasundaran M, Schiffer C; Univ. of Massachusetts Med. Sch., Worcester, USA BACKGROUND: HIV-1 Vif is essential for replication in vivo and in nonpermissive cells. Recent reports have shown that one of the functions of Vif is to degrade the antiretroviral protein APOBEC3G found in nonpermissive T-cell lines. APOBEC3G, a cytidine deaminase, induces C to U change in the minus strand cDNA which re |
| 355 | The Sequence of Proviruses Resulting from Vif-defective HIV-1 Infection Supports Direct APOBEC3G Deamination of Minus-strand DNA during Reverse Transcription. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 355) Bouchonnet F, Lecossier D, Clavel F, Hance AJ; INSERM U552, Paris, France BACKGROUND: Incorporation of the cytosine deaminase APOBEC3G into HIV particles, which is inhibited by the Vif accessory protein, induces G to A mutations into viral plus-strand DNA. These mutations are thought to result from the introduction of C to U changes in newly synthesized minus-strand DNA, but alternatives hav |
| 356 | Mapping the Restriction Determinants in HIV-1 Capsid and Defining the Role of Cyclophilin A in Restriction. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 356) Hatziioannou T, Cowan S, Bieniasz PD; Aaron Diamond AIDS Res. Ctr., New York, NY, USA BACKGROUND: Host susceptibility to retroviral infection is influenced by dominant restriction factors such as Fv1 in mice, Ref1 in humans and Lv1 in primates that block infection by targeting the viral capsid at an early post-entry step. The resistance conferred by these factors can be quite substantial but can be abro |
| 357 | Natural Resistance of HIV-1 Primary Isolates to Ref1. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 357) Bobardt M, Saphire A, Gallay P; Scripps Res. Inst., La Jolla, CA, USA BACKGROUND: Mammalian cells contain restriction factors that confer resistance to retroviral infection. The restriction factor called Ref1 confers human cells resistance to N-MLV and EIAV, but not to B-MLV or any primate lentiviruses. The current hypothesis is that Ref1 blocks viral infection at a post-entry step by ac |
| 358 | ARF-1 Independent Attachment of AP Complexes to Endosomal Membranes by HIV-1 Nef Correlates with Virologic Function. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 358) Guatelli J, Hitchin D, Noviello C, Coleman S, Madrid R, Benichou S; San Diego VA Healthcare System, CA, USA BACKGROUND: HIV-1 Nef influences the endosomal system by interacting with the cellular adaptor protein (AP) complexes, which mediate the formation of transport vesicles and their selective inclusion of transmembrane proteins. The interaction of Nef with AP complexes depends on a typical leucine-based sorting motif of s |
| 359 | Polymorphisms in Cellular Restriction of HIV-1 Infection. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 359) Ciuffi A, Bleiber G, Munoz M, Martinez R, Meylan P, Bonhoeffer S, Trono D, Telenti A; Univ. of Lausanne, Switzerland BACKGROUND: The HIV life cycle is characterized by numerous interactions with host cellular proteins. Interindividual differences in susceptibility to HIV infection may result from (genetic) polymorphism in host factors participating in the viral life cycle. We (i) defined the variability in permissiveness of CD4 cells |
| 360 | Inhibition of HIV-1 Replication by a Novel Domain of Sam68, the 68-Kilodalton Src-associated Protein In Mitosis. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 360) Zhang J, Liu Y, Li J, He JJ; Indiana Univ. Sch. of Med., Indianapolis, USA and 2Walther Cancer Inst., Indianapolis, IN, USA BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) replication requires active nuclear export of incompletely spliced and unspliced HIV-1 viral RNAs, which is accomplished by HIV-1 Rev. Evidence has accumulated to suggest that Sam68 plays a role in Rev-dependent nuclear export of those intro-containing HIV-1 RNAs. |
| 361 | A DEAD Box Protein Facilitates HIV-1 Replication as a Critical Cellular Co-factor of Rev. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 361) Pomerantz R, Fang J, Kubota S, Yan B, Zhou N, Zhang H, Godbout R; Thomas Jefferson Univ., Philadelphia, PA, USA and 2Univ. of Alberta, Canada BACKGROUND: HIV-1 Rev escorts unspliced viral mRNAs out of the nucleus of infected cells, which allows formation of infectious HIV-1 virions. We have identified a putative RNA helicase, DDX1, as a novel cellular co-factor which interacts with a specific motif of Rev, entitled nuclear diffusion inhibitory signal. METHOD |
| 362 | INI/hSNF5 Mediates Specific Incorporation of Components of Sin3A-HDAC Complex into HIV-1 Virions. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 362) Sorin M, Davies K, Cheng G, Kalpana GV; Albert Einstein Coll. of Med., Bronx, NY, USA BACKGROUND: INI1/hSNF5, a component of the chromatin remodeling SWI/SNF complex, and a tumor suppressor, directly interacts with HIV-1 integrase. We previously demonstrated that truncated version of INI1/hSNF5, containing minimal IN-binding domain, trans-dominantly inhibits HIV-1 particle production. Tumor-derived INI- |
| 363 | Changes in the Ratio of P-TEFb Complexes Correlates with a Reduction in HIV Replication. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 363) Biglione S, Byers S, Shutt D, Price D, Maury W; Univ. of Iowa, Iowa City, USA BACKGROUND: The HIV promoter (LTR) utilizes the cellular complex P-TEFb during transcription. A large form of the complex (composed of CDK9, cyclin T1, Hexim 1 and 7SK) and a small form (CDK 9, cyclin T1) exist within the cell and cellular genes have been shown to preferentially utilize the small form for transcription |
| 364 | Small Heat Shock Proteins as Innate Antiviral Factors Counteracted by HIV-1 Viral Protein R. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 364) Zhao Y, Benko Z, Liang D, Hou J, Chiu K, Agbottah E, Yu M, Innis S, Reed P, Kabat W, Elder RT, Zarzio PD, Taricani L, Young PG, Bukrinsky M; Northwestern Univ., Chicago, IL, USA BACKGROUND: Cells have developed various innate antiviral defense mechanisms to resist HIV-1 invasion. The host innate response typically recognizes highly conserved retroviral determinants. Even though viral protein R (Vpr) is a highly conserved lentivirus protein, there is no published evidence indicating a similar h |
| 365 | Role of SHP-1 Deregulation in HTLV-1 Leukemogenesis. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 365) Cheng J, Kydd A, Noonan K, Xu C, Murakami A, Marasco W; Dana-Farber Cancer Inst., Boston, MA, USA BACKGROUND: Human T-cell lymphotropic virus (HTLV-1) is the etiological agent for adult T-cell Leukemia (ATL). Past studies have provided evidence that deregulations of IL-2 receptor signaling may play an important role in the events that lead to immortalization and oncogenic transformation of CD4+ T-cells by HTLV-1. W |
| 366 | Niemann Pick Type C: an Important Protein during HIV Infection. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 366) Leao IC, Hildreth JE; Johns Hopkins Sch. of Med., Baltimore, MD BACKGROUND: Niemann Pick type C (NPC) is a rare neurovisceral disorder caused by mutations in the NPC protein. This protein is located in late endosomes and is responsible for the post-lysosomal trafficking of cholesterol. NPC mutant cells are characterized by marked accumulation of unesterified cholesterol and sphingo |
| 367 | alpha-Defensin-1 Inhibits HIV-1 following Entry and Involves PKC Signaling Pathway. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 367) Chang TL, Vargas J Jr, Lukay A, Klotman ME; Mount Sinai Sch. of Med., New York, NY, USA BACKGROUND: alpha-Defensins are highly abundant antimicrobial peptides in polymorphonuclear leukocytes and play an important role in innate immunity. Recent studies including ours have shown that human alpha-denfesin-1 is a potent inhibitor against HIV-1. Here we examined the molecular mechanism of alpha-defensin-1-med |
| 368 | Global Perturbations of Gene Expression by HIV-1 in Monocyte-derived Macrophages: Synergistic Induction and Repression of Genes Mediating Cell Cycle Arrest. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 368) Brown J, Coberley C, Kohler J, Craig H, Sleasman J, Goodenow M; Univ. of Florida Coll. of Med., Gainesville, USA and 2All Children's Hosp., Univ. of South Florida, St. Petersburg, USA BACKGROUND: CD4+ macrophages are susceptible to HIV-1 infection, have a long half-life in tissues, and represent a viral reservoir that may elude antiretroviral treatment. We designed a study to discover sentinel genetic networks impacted by HIV-1JRFL interaction with primary monocyte-derived macrophages (MDM). We hypo |
| 369 | Regulation of Cholesterol Biosynthesis during Viral Infections. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 369) Wout AB, Swain JV, Peng T, Pathmajeyan MS, Bumgarner RE, Mullins JI; Univ. of Washington, Seattle, USA BACKGROUND: Recent studies by several laboratories have highlighted the importance of cholesterol in the human immunodeficiency virus type 1 (HIV-1) life cycle. Removing cholesterol from virions or inhibition of cholesterol biosynthesis with lovastatin inhibits HIV-1 production in vitro. This inhibition is thought to b |
| 370 | Activation by Inflammatory Stimuli Increases Neutrophil Binding of HIV-1 and Increases Infection of Lymphocytes by the Neutrophil-bound HIV-1. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 370) Gabali A, Anzinger J, Spear G, Thomas L; Rush Univ. Med. Ctr., Chicago, IL, USA BACKGROUND: Previous studies demonstrated that resting neutrophils bind HIV-1 (HIV) and that neutrophil-bound HIV is more infectious than free virus for lymphocytes. The present study was performed to determine the effect of neutrophil activation on HIV binding by neutrophils and on the subsequent infection of lymphocy |
| 371 | Transactivation Potency of HIV-1 Tat in the Viral Latent Reservoir. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 371) Mabery E, Irwin D, Limketkai B, Peterlin M, Romeo J; San Francisco State Univ., CA, USA and 2Univ. of California, San Francisco, USA BACKGROUND: Studies on HIV dynamics in vivo have shown that cells expressing high levels of viral RNA are rapidly cleared while cells expressing low levels persist. Treatment of patients with HAART results in the accumulation of such long-lived cryptically infected cells. METHODS: Since the HIV transactivator, Tat, con |
| 372 | Latent HIV-1 Genomes Reside in Actively Transcribed Genes in Resting CD4+T Cells n vivo. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 372) Han Y, Monie D, Sedaghat A, Shimoji S, Liu X, Pierson T, Margolick J, Siliciano R, Siliciano J; Johns Hopkins Univ. Sch. of Med., Baltimore, MD, USA and 2Johns Hopkins Univ. Sch. of Publ. Hlth., Baltimore, MD, USA BACKGROUND: HIV-1 persists in latently infected resting memory CD4+ T cells carrying an integrated copy of the viral genome. This stable reservoir represents a major barrier to HIV-1 eradication in infected individuals. One mechanism for HIV-1 latency is proviral integration into chromosomal sites that are repressive f |
| 373 | A Promoter Targeted dsRNA Induces HIV-1 Gene Silencing and de novo CpG Methylation. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 373) Suzuki K, Suter C, Shijuuku T, Fukamachi T, Zaunders J, Ku S, Cheong K, Ward R, Guillemin G, Martin D, Cooper D, Kelleher A; St. Vincent's Hosp., Sydney, Australia BACKGROUND: Short double-stranded RNA (dsRNA) targeting structural and regulatory genes of HIV-1 have been shown to induce RNA interference acting via a specific mRNA degradation pathway, resulting in post transcriptional gene silencing (PTGS). In plants dsRNA can also induce gene silencing via transcriptional gene sil |
| 374 | Inhibition of HIV-1 Replication Using tat-specific Micro-RNA. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 374) Boden D, Pusch O, Lee F, Tucker L, Ramratnam B; Brown Univ. Med. Sch., Providence, RI, USA BACKGROUND: Post-transcriptional silencing of HIV-1 replication can be achieved by RNA interference. The cellular expression of short interfering RNA (siRNA) or short hairpin RNA (shRNA) homologous to regions of the HIV-1 genome decreases viral replication by the selective degradation of the target RNA. Here, we demons |
| 375 | The Mechanism of HIV-1 VPR-mediated G2 Arrest: Roles of the Host Cell DNA Damage Signaling Pathway. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 375) Zimmerman E, Walker J, Planelles V; Univ. of Utah, Salt Lake City, USA BACKGROUND: HIV-1 Vpr induces G2 cell cycle arrest in infected CD4+ cells. Vpr mediates this effect via activation of the host cell ATR-dependent DNA damage pathway. However, the mechanism of ATR activation by Vpr is poorly understood. When ATR-dependent G2 arrest is induced in response to genotoxic stress, it is known |
| 376 | HIV-1 Nef Modulation of Vpr-induced Apoptosis. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 376) Andersen J, Aldrovandi G, Dehart J, Planelles V; Univ. of Utah, Salt Lake City, USA and 2Univ. of Alabama at Birmingham, USA BACKGROUND: The human immunodeficiency virus type-1 (HIV-1) encodes four accessory genes (vpr, vpu, vif and nef) that regulate host cell biology. Vpr induces cell cycle arrest in G2 followed by apoptosis. Nef has been reported to exert both pro- and anti-apoptotic effects when expressed in mammalian systems. To evaluat |
| 377 | The Down-regulation of Interferon Genes by HIV-1 Nef in Primary CD4+ T Cells. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 377) Woelk C, Sasik R, Rought S, Plotkin C, Du P, Corbeil J; Univ. of California, San Diego, USA and 2VMRF, San Diego, CA, USA BACKGROUND: The effect of nef expression upon primary CD4+ T cells was investigated using high-density oligonucleotide microarrays. METHODS: Primary CD4+ T cells were purified from whole blood of healthy donors by negative depletion methods. Electroporation was used to introduce wild-type nef (NL4-3) expression plasmid |
| 378 | Heat Shock Protein 70 Counteracts Activity of the HIV-1 Viral Protein R. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 378) Iordanskiy S, Zhao Y, Bukrinsky M; George Washington Univ., Washington, DC, USA and 2Northwestern Univ., Chicago, IL, USA BACKGROUND: HIV-1 Vpr is an important contributor to viral pathogenesis. Vpr displays several highly conserved pathogenic activities, including induction of cell cycle G2 arrest and cell death, as well as stimulating HIV-1 infection of macrophages. To identify innate anti-Vpr factors, we performed a genetic search for |
| 379 | Full Molecular Characterization of Simian Immunodeficiency Virus Infecting Talapoins Monkeys: Evidence for a New SIV Lineage in Miopithecus Species. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 379) Courgnaud V, Liegeois F, Switzer WM, Loul S, Mpoudi-Ngole E, Delaporte E, Peeters M; UR36, Inst. of Res. and Devt. and Univ. of Montpellier I, France BACKGROUND: Primate lentiviruses are a diverse group that naturally infect at least 33 nonhuman African primate species. Initially, 6 distinct lineages (SIVcpz, SIVsm, SIVagm, SIVsyk, SIVlhoest, and SIVcol) have been described. More recently, a number of potential recombinant lineages have been also described highlight |
| 380 | Endemic SIVsm Infection in Wild-living Sooty Mangabeys. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 380) Santiago ML, Range F, Bibollet-Ruche F, Fruteau C, Peho R, Brookfield JF, Noe R, Sharp PM, Shaw GM, Hahn BH; Univ. of Alabama at Birmingham, USA BACKGROUND: Sooty mangabeys harbor simian immunodeficiency viruses (SIVsm) that have crossed to humans on at least 7 occasions to yield the diverse groups of HIV-2 (A-G). However, data on SIVsm genetic diversity in wild SM populations is limited, and it is unclear how SIVsm infection is maintained in its natural host. |
| 381 | A Comparative Study of Adaptive Molecular Evolution in Different HIV Groups and Subtypes. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 381) Choisy M, Woelk CH, Guegan JF, Robertson DL; CNRS / IRD, Montpellier, France BACKGROUND: The development of candidate HIV vaccines demands a thorough investigation into the consistency of the selective environment - presumed primarily to be due to the host immune response - between divergent HIV lineages. This study aims to explore whether there are differences in the location and intensity of |
| 382 | CTL Responses as Major Selective Forces Shaping the Course of HIV-1 Evolution in vivo. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 382) Liu Y, Zhao H, Genowati I, McNevin J, Nickle DC, Shriner D, Wong K, Cao J, Davis K, Rose L, McElrath MJ, Mullins JI; Univ. of Washington, Seattle, USA and 2Fred Hutchinson Cancer Res. Ctr., Seattle, WA, USA BACKGROUND: CD8+ cytotoxic T-lymphocyte (CTL) responses are thought to be critical for controlling HIV-1 infection. CTL escape mutants have been detected during both acute and chronic infection. However, the magnitude of this response, relative to other selective forces that may shape the evolving HIV-1 population, hav |
| 383 | African Origin of STLV-I in TNPRC Captive Sooty Mangabey Colony. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 383) Traina-Dorge V, Lorino R, Metzger M, Marx P, Apetrei C; Tulane Natl. Primate Res. Ctr., Covington, LA, USA BACKGROUND: A serological and molecular survey to evaluate prevalence of STLV infection and STLV diversity within the Tulane National Primate Research Center (TNPRC) captive sooty mangabey colony (Cercocebus atys) was conducted. Colony animals were originally obtained from the Yerkes Primate Research Center (YNPRC) bet |
| 384 | env Sequences and Neutralization of HIV from Transmission Partners of Primary HIV Infection. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 384) Little SJ, Liu Y, Wrin T, Frost SD, Chappey C, Smith DM, Petropoulos CJ, Richman DD; Univ. of California, San Diego, USA BACKGROUND: To evaluate 10 subjects with recent HIV infection and the 8 sexual partners who transmitted virus to them, env sequences and HIV-specific neutralizing antibody responses to virus recovered from blood of both the HIV donor and recipient were characterized. METHODS: We identified 10 subjects with primary HIV |
| 385 | Primary HIV-1 Infection is Clonal in a Minority of Women from Africa. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 385) Sagar M, Kirkegaard E, Lavreys L, Overbaugh J; Fred Hutchinson Cancer Res. Ctr., Seattle, WA, USA BACKGROUND: HIV-1 envelope sequences are genetically diverse in about 60% of heterosexually infected women from Africa, within a few months after infection, but they are homogeneous in the remaining women. To understand the selection mechanism during heterosexual transmission of HIV-1, we examined the genetic diversity |
| 386 | HIV-1 V1/V2 and V3 env Diversity during Primary Infection Suggests a Role for Multiply Infected Cells in Transmission. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 386) Ritola K, Pilcher C, Little S, Fiscus S, Hicks C, Eron J, Richman D, Swanstrom R; Univ. of North Carolina at Chapel Hill, USA BACKGROUND: Sexual transmission of HIV-1 is thought to be a low probability event resulting in a genetically less complex virus population in the recipient than is found in the transmitter. Studies measuring the genetic complexity of the initial virus population have reported homogeneous and/or heterogeneous virus popu |
| 387 | Consistent Recovery of Fully Infectious HIV-1 from Infected Seronegative Children Receiving Combination Antiretroviral Therapy from Early Infancy. Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 387 Persaud D, Kajdas J, Watson D, Siliciano R; Johns Hopkins Univ. Sch. of Med., Baltimore, MD, USA and 2Univ. of Maryland Sch. of Med., Baltimore, USA BACKGROUND: The establishment of reservoirs for HIV provides a barrier to the eradication of virus from treated individuals. One reservoir of viral persistence is the resting CD4+ memory T-cell carrying latent HIV. Studies in chronically-infected children and adults show that the number of latently infected cells is ap |
| 388 | Higher CD4+ T Cell Counts Associated with Low Viral pro/pol Replication Capacity among Treatment Naïve Adults in Early HIV-1 Infection. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 388) Barbour JD, Segal MR, Wrin T, Ramstead CA, Liegler TJ, Petropoulos CJ, Hecht FM, Grant RM; Gladstone Inst. of Virology and Immunology, San Francisco, CA, USA BACKGROUND: Drug resistant HIV-1 may be of lowered replication capacity, and in vivo virulence, leading to preservation of CD4 counts among individuals in virologic failure of anti-retroviral therapy (ART). We sought to determine if low pro/pol replication capacity (RC) accounted for higher CD4 T cell counts, if there |
| 389 | Intermittent Low-Level Viremia During the Eclipse Phase of Primary HIV-1 Infection. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 389) Fiebig EW, Heldebrant C, Smith R, Conrad A, Delwart EL, Busch MP; Univ. of California, San Francisco, USA BACKGROUND: To determine if HIV is present during the eclipse phase of primary HIV infection, i.e., the period between exposure and the onset of quantifiable, sustained viremia. METHODS: Anonymized panels consisting of plasma samples collected on average twice weekly from source plasma donors newly infected with HIV we |
| 390 | Oral Transmission of SIV Indicates Entry across the Oral and Esophageal Mucosa Followed by Rapid Dissemination. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 390) Milush J, Kosub D, Schmidt K, Scott F, Brown C, Westmoreland S, Marthas M, Sodora D; Univ. of Texas Southwestern Med. Ctr., Dallas, USA BACKGROUND: The majority of HIV infections occur via transmission of the virus across a mucosal surface. HIV infection following oral exposure has been documented during both mother-to-child and oral-genital transmission. The goal of this study was to utilize the SIV/macaque animal model to assess the sites of entry an |
| 391 | Phylogenetic Relationships between HIV-1 Viruses from Seroconverters across Europe. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 391) Gifford R, Cane P, Back N, Fleury H, Nielsen C, Ortiz M, Balotta C, Porter K, Pillay D; Univ. Coll. London, UK BACKGROUND: HIV subtype B predominates the epidemic in Western Europe, particularly in homosexual men and ineighbor-joiningecting drug users. Little is known, however, about the transmission dynamics between European countries especially as risk group profiles have changed in recent years. We examined the phylogenetic |
| 392 | Molecular and Epidemiological Characteristics of Primary HIV-1 Infections among a Cohort of Predominantly Men Who Have Sex with Men in a Defined Geographical Area: Transmission Events Associated with High Risk Activity and STD. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 392) Pao D, Fisher M, Hue S, Dean G, Cane P, Sabin C, Pillay D; Brighton and Sussex Univ. Hospitals, UK BACKGROUND: It is postulated that onward transmission of HIV-1 is increased during primary HIV infection (PHI) due to high viral load, high-risk sexual behavior and increased rates of concurrent sexually transmitted diseases (STD). In a treatment center with a high population of MSM and high rates of both HIV and STD, |
| 393 | Immunodominance of HIV-1 Nef-specific CD8+ T-cell Responses in Acute HIV-1 Infection. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 393) Lichterfeld M, Yu XG, Cohen D, Addo MM, Malenfant J, Johnston MN, Strick D, Allen T, Rosenberg ES, Walker BD, Altfeld M; Massachusetts Gen. Hosp., Harvard Med. Sch., Boston, MA, USA BACKGROUND: Acute HIV infection is associated with the emergence of a CD8+ T-cell response that coincides with the initial drop in peak viremia, but the targets of these early responses and their relationship to responses in chronic infection are not well defined. METHODS: To determine the specificity of HIV-1-specific |
| 394 | Initial Immune Control of HIV-1 followed by Superinfection and Failure: Significance of CTL Specificity. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 394) Daar ES, Yang OO, Jamieson BD, Smith DM, Pitt JA, Petropoulos CJ, Richman DD, Little SJ, Leigh Brown AJ; Harbor-UCLA Med. Ctr., Univ. of California, Los Angeles, USA BACKGROUND: In a patient with PHI, initially infected with a B subtype MDR virus (strain A), loss of drug resistance at 6 months post-infection was associated with outgrowth of a distinct B subtype strain. We hypothesized that the initial control of viremia (set point 1000 copies/mL) did not extend to the superinfectin |
| 395 | Structured Treatment Interruptions in Primary HIV Infection: Final Results of the Multicenter Prospective PRIMSTOP Pilot Trial. Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 395 Hoen B, Fournier I, Charreau I, Lacabaratz C, Burgard M, Arvieux C, Bouvet E, Pariente F, Aboulker JP, Venet A, Rouzioux C, Raffi F, the Primstop study group; Univ. Hosp., Besancon, France BACKGROUND: PRIMSTOP (ANRS 100), a multicenter, prospective trial, evaluated the ability of structured treatment interruptions to induce anti-HIV immune response and to control HIV replication following HAART discontinuation in patients with primary HIV infection. METHODS: Patients with early acute symptomatic primary |
| 396 | Determination of HIV-specific CD8+ and CD4+ Responses in Structured Treatment Interruptions in Primary HIV Infection: Results of the Multicenter Prospective Pilot Trial PRIMSTOP. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 396) Lacabaratz-Porret C, Hoen B, Urrutia A, Rodallec A, Compagnucci A, Burgard M, Rouzioux C, Venet A; INSERM E0109, Univ. Paris Sud, Le Kremlin Bicetre, France BACKGROUND: The PRIMSTOP (ANRS 100) prospective trial evaluated the ability of structured treatment interruptions to induce anti-HIV immune response and to control HIV replication after HAART discontinuation in patients with primary HIV infection. METHODS: Patients were given a 34-week continuous HAART with hydroxyurea |
| 397 | HIV-1 RNA Viral Load Dynamics after Discontinuation of Early and Effective HAART Initiated During Primary HIV-1 Infection. Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 397 Desquilbet L, Goujard C, Deveau C, Sinet M, Chaix ML, Venet A, Rouzioux C, Delfraissy JF, Meyer L, PRIMO Study Group; Le Kremlin Bicetre, France and 2Paris, France BACKGROUND: In the context of HAART regimen interruption, our objectives were: to estimate viral load within the year following interruption of HAART initiated among 58 primary HIV-1-infected subjects enrolled in the prospective PRIMO Cohort; to compare this viral load with viral load reached spontaneously at the same |
| 398 | Clinical Characteristics and Treatment Uptake in Patients Newly Infected with HIV Identified over a 1-year Period: The Phaedra Collaborative Cohort. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 398) Ramacciotti T, Smith D, Johnston M, Pae E, Bloch M, Rosenberg E, Kaldor J, Walker BD; Natl. Ctr. in HIV Epidemiology and Clin. Res., Univ. of New South Wales, Sydney, Australia BACKGROUND: The clinical value of initiating antiretroviral (ARV) therapy during primary HIV infection is unclear. To determine whether baseline patient characteristics influenced the decision to start ARV therapy we collected data on patients identified with PHI over a one year period. The primary outcome measure was |
| 399 | Virological and Immunological Predictors of Time to Initial Viral Suppression and Viral Rebound in a Randomised Trial of Combination Therapy in Primary HIV Infection followed by Treatment Interruption. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 399) Smith D, Grey P, Petoumenos K, Zaunders J, Kelleher A, Cunningham P, Carr A, Bloch M, Finlayson R, McFarlane R, Kaldor J, Cooper D; Natl. Ctr. in HIV Epidemiology and Clin. Res., Univ. of New South Wales, Sydney, Australia BACKGROUND: Induction therapy followed by treatment interruption has been examined as a strategy in patients identified in primary HIV infection. We analyzed whether pre-treatment clinical, virological, or immunological variables were associated with more rapid viral suppression on therapy, and subsequently delayed vir |
| 400 | Long-term Control of HIV-1 RNA Replication following a Unique Supervized Treatment Interruption and Mycophenolate Mofetil Therapy in Patients Treated with HAART since Primary HIV-1 Infection. Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 400 Rizzardi GP, Guaraldi G, Lazzarin A, Pantaleo G, Tambussi G; HSR Hosp San Raffaele, Milan, Italy BACKGROUND: Mycophenolate mofetil (MMF) reduces the pool of dividing and activated CD4+ T cells, contributing to control virus load. Impact on VIRUS LOAD and CD4+ T cell counts of a unique supervised treatment interruption coupled with MMF is assessed in a non-randomised controlled study. METHODS: Since primary HIV-1 i |
| 401 | Association of CCR5 Promoter Human Haplogroup E with Faster HIV-1 Disease Progression among Injection Drug Users in Thailand. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 401) Yang C, Nguyen L, Chaowanachan T, Vanichseni S, Li M, Mock PA, Griensven FV, Martin M, Sangkum U, Choopanya K, Tappero JW, Lal RB, Hu DJ; CDC, Atlanta, GA, USA BACKGROUND: The discovery that chemokine receptors are used by HIV-1 as co-receptors for cellular entry led to the finding that host genetic factors can influence the susceptibility to HIV-1 infection and disease progression. However, most studies have focused on European or North American populations. In the present s |
| 402 | Causal Mechanisms of the Effects of Age and the CCR-Delta32, CCR-64I, and SDF-1 3'A Alleles on AIDS Development. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 402) Geskus R, Meyer L, Hubert B, Schuitemaker H, Berkhout B, Rouzioux C, Theodorou I, Delfraissy FJ, Prins M, Coutinho R; Municipal Hlth. Svc., Amsterdam, The Netherlands BACKGROUND: Several studies have investigated and confirmed the effects of age and the CCR5-Delta32, CCR2-64I and SDF-1 3 A alleles on HIV-1 disease progression. Of interest are the causal mechanisms by which these cofactors influence progression to AIDS. METHODS: We used longitudinal data from 2 cohort studies among h |
| 403 | HLA-DRB1, -DQB1, and HLA-B Associations with Early HIV-1 Viral Load in Seroconverters from the Multicenter AIDS Cohort Study. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 403) Kaslow RA, Tang J, Gao X, Cloud G, Makhatadze N, Detels R, O'Brien S, Carrington M; Univ. of Alabama at Birmingham, USA BACKGROUND: HLA class I polymorphisms modulate early response to HIV-1 infection and its ultimate outcome. In contrast, the role of variation in HLA class II genes in modulating early or late infection has been elusive, and joint effects of haplotypes extending from class I to class II have not been described. We analy |
| 404 | HIV Infection and Disease Progression Are Not Accelerated by the MCP-1-2578G Mutant Allele in the ANRS SEROCO Cohort. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 404) Meyer L, Casanova S, Persoz A, Rouzioux C, Theodorou I, Delfraissy JF, Combadiere C; Le Kremlin Bicetre, France and 2Paris, France BACKGROUND: MCP-1 (monocyte chemoattractant protein-1, a CCR2 ligand) could play a central role in establishment and spread of HIV-1 infection. The objective of this study is to assess the role of a polymorphism in the gene promoter of MCP-1, the -2578G allele, in spontaneous HIV disease progression. METHODS: All 419 H |
| 405 | The Effect of Escape Mutations upon Disease Progression in HLA B27 Positive Individuals within The Australian Long-term Non-progressor Cohort. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 405) Ammaranond P, Guerin J, Anderson B, Doong C, Finlayson R, Kelly M, McMurchie M, Price R, Cooper D, Kelleher A; Natl. Ctr. in HIV Epidemiology and Clin. Res., Univ. of New South Wales, Sydney, Australia BACKGROUND: HLA B27 is associated with long-term non-progression and is characterized by a CTL response to a conserved epitope in Gag p24 (KRWIILGLNK 263 to 272). The HLA B27 restricted epitope like almost all HLA B27 restricted epitopes has an arginine at position 264 (R264) that is essential for high affinity binding |
| 406 | HLA Class 1 Genotype and HIV Genome Evolution During Primary Infection. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 406) Bernardin F, Baxter-Lowe LA, Peddada L, Delwart E; Blood Systems Res. Inst., San Francisco, CA, USA BACKGROUND: The rapid emergence of HIV and SIV CTL escape mutants has been described. Host factors such as HLA class 1 genotypes are expected to influence the site of such mutations. HIV genomes from African-Americans undergoing seroconversion were sequenced to identify the gene products under the strongest selective p |
| 407 | The Breadth and Magnitude of T-lymphocyte Responses to HIV-1 Antigens Are Associated with Cytokine Gene Polymorphisms. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 407) Song W, Tang J, Goepfert PA, Wang C, Bansal A, Sabbaj S, Mulligan MJ, Wilson CM, Kaslow RA; Univ. of Alabama at Birmingham, USA BACKGROUND: Adaptive immune responses are orchestrated by a large number of cytokines that are often expressed at highly variable levels. We searched for the independent effects of cytokine gene variations on HIV-specific T-cell responses. METHODS: In 88 HIV-1-seropositive youth with fully resolved HLA profile, interfe |
| 408 | Fas and Fas Ligand Polymorphisms Influence the Rise in CD4+ T-cell Count after Antiretroviral Therapy in Drug-naïve HIV+ Patients. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 408) Nasi M, Pinti M, Bugarini R, Troiano L, Lugli E, Bellodi C, Mussini C, Borghi V, Esposito R, Cossarizza A; Univ. of Modena and Reggio Emilia and Azienda Policlin., Italy BACKGROUND: We studied the influence of polymorphisms of Fas (CD95) and Fas Ligand (CD178) (FasL) genes on CD4+ T lymphocyte count and viral load following initiation of treatment of human immunodeficiency virus (HIV) infection. METHODS: We analyzed polymorphisms from 131 drug-naïve HIV+ patients and 136 healthy donors |
| 409 | Intrinsic Obstacles to HIV Co-receptor Switching. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 409) Mosier DE, Pastore C, Ramos A, Geerdes D; Scripps Res. Inst., La Jolla, CA, USA BACKGROUND: As few as 1 or 2 amino acid changes in envelope can change the co-receptor use of HIV-1 from CCR5 to CXCR4. Given the high mutation rate of HIV-1, co-receptor switch variants should be readily generated, but CXCR4-using (X4 or R5X4) viruses take years to emerge in a subset of infected individuals. We hypoth |
| 410 | Tissue-derived SHIV from Late Stage Animals Are Macrophage Tropic and Use CXCR4 for Infections of both Rhesus Macaque PBMC and Alveolar Macrophage. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 410) Imamichi H, Donau OK, Igarashi T, Dumaurier MJ, Sadjadpour R, Plishka RJ, Buckler-White A, Buckler C, Suffredini AF, Lane HC, Moore JP, Martin MA; SAIC-Frederick, Inc., MD, USA BACKGROUND: Highly pathogenic SIV/HIV chimeric viruses (SHIVs) cause rapid, irreversible, and systematic depletion of CD4+ T lymphocytes in rhesus monkeys. In the absence of this T cell subset, virus production is sustained for several months by tissue macrophage. We recently reported that viral variants present in pla |
| 411 | Macrophage Tropism of SIVsm Is Maintained in Progressive Disease, but Decreases in Infected Macaques that Do Not Progress to Disease. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 411) Nordqvist A, Fredlund H, Vodros D, Thorstensson R; Lund Univ., Sweden and 2Swedish Inst. for Infectious Disease Control, Stockholm, Sweden BACKGROUND: To compare coreceptor use and macrophage tropism of sequential SIVsm reisolates in relation to the severity of SIVsm infection, following intravenous or intrarectal inoculation of cynomolgus macaques. METHODS: Cynomolgus macaques were infected with SIVsm (sooty mangabey origin) either by the intravenous or |
| 412 | Molecular Determinants for Decreasing Sensitivity to Coreceptor Antagonists of Evolving R5 and X4 Virus Variants in Natural Course of Infection. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 412) Schuitemaker H, Koning F, Stalmeijer E, Navis M, Dekker J, Boeser-Nunnink B, Rij R; Sanquin Res. and Univ. of Amsterdam, The Netherlands BACKGROUND: Entry of HIV-1 into a target cell is initiated by the binding of the envelope glycoprotein gp120 to CD4 and a coreceptor, in general CCR5 or CXCR4. We previously observed that with progression of disease R5 and X4 variants became less susceptible to inhibition by antagonists directed against CCR5 and CXCR4, |
| 413 | CD4 Signaling in Primary Human Macrophages is Through the ERK-1/2 MAP Kinase Pathway. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 413) Tomkowicz B, Lee CH, Yi Y, Collman RG; Univ. of Pennsylvania, Philadelphia, USA BACKGROUND: CD4 plays a central role in immune function and as the primary receptor for HIV-1. Infection is initiated by binding of gp120 to CD4 and a G-protein coupled co-receptor, either CCR5 (R5 strains) or CXCR4 (X4 strains). CD4 lacks intrinsic kinase activity. In lymphocytes, engagement of CD4 leads to activation |
| 414 | HIV-1-mediated Apoptosis Occurs in Macrophages Infected by X4, but Not by R5 Viruses. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 414) Aquaro S, Ranazzi A, Bellocchi M, Guenci T, Saccomandi P, Giannella S, Schols D, Garaci E, Calio R, Perno CF; Univ. of Rome Tor Vergata, Italy and 2Rega Inst. for Med. Res., Leuven, Belgium BACKGROUND: HIV-1 binding with CXCR4 is associated with functional responses (including apoptosis induction) in different cellular target cells, but the role of this co-receptor is poorly understood in monocytes/macrophages (M/M), that are a crucial reservoir of HIV-1. M/M similarly express both HIV co-receptors, CXCR4 |
| 415 | Genotypic Potential for Syncytium Induction Characterizes Early V3 Loop Evolution in Singly and Dually-infected Individuals with Rapid HIV Disease Progression. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 415) Jensen MA, Gottlieb GS, Wout AB, Wong KG, Margolick JB, Mullins JI; Univ. of Washington, Seattle, USA and 2Johns Hopkins Sch. of Hygiene and Publ. Hlth., Baltimore, MD, USA BACKGROUND: HIV that uses the CXCR4 coreceptor for T-cell entry (X4), or that induces syncytia on indicator cells (SI), has been associated with accelerated progression of HIV disease. Concordance between SI and X4 states is high, but not perfect. Anecdotal evidence suggests that unusually early outgrowth of, or infect |
| 416 | Characterization of DC-SIGN and DC-SIGNR Transcript Isoforms in Human Vaginal and Rectal Mucosa. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 416) Liu H, Hladik F, Andrus T, Nelson P, Sakchalathorn P, Lentz G, Corey L, McElrath MJ, Zhu T; Univ. of Washington Sch. of Med., Seattle, USA and 2Fred Hutchinson Cancer Res. Ctr., Seattle, WA, USA BACKGROUND: Dendritic cells may capture HIV-1 in mucosa and transmit it to target cells in trans by DC-SIGN. A close homologue of DC-SIGN, DC-SIGNR, exhibits similar HIV-1 capturing capacity. It has been demonstrated that alternative splicing of DC-SIGN and DC-SIGNR pre-mRNA generates a wide repertoire of transcripts e |
| 417 | Lack of SIV Target Cells in African Non-human Primate: Host or Virus Adaptation? Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 417) Pandrea I, Apetrei C, Dufour J, Mefford M, Bohm R, Marx P, Lackner A, Veazey R; Tulane Natl. Primate Res. Ctr., Covington, LA, USA BACKGROUND: African hosts of SIV are considered resistant to disease progression despite persistent high viral loads. In pathogenic models, the gastrointestinal tract is the major site of viral replication and CD4+T cell depletion in SIV infection, and the major target cells in early infection are CD4+CCR5+CD45RA-. The |
| 418 | Differences in Dendritic Cell Populations and Signaling May Account for Divergent SIV Infection Outcomes in Rhesus Macaques and Sooty Mangabeys. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 418) Barry AP, Chavan R, Wernett M, McCausland M, Staprans S, Silvestri G, Feinberg MB; Emory Univ., Atlanta, GA, USA BACKGROUND: Pathogenic SIV infection of rhesus macaques is characterized by chronic high viremia, generalized immune system (especially CD8+ T cell) activation and progressive CD4+ T cell depletion. In contrast, SIV infection in sooty mangabeys (natural host species) is characterized by near normal CD4+ T-cell counts, |
| 419 | Parallel Rather Than Sequential Targeting of Intraepithelial Langerhans and T Cells during Vaginal HIV-1 Transmission. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 419) Hladik F, Sakchalathorn P, Ballweber L, Lentz G, Eschenbach D, McElrath MJ; Fred Hutchinson Cancer Res. Ctr., Seattle, WA, USA and 2Univ. of Washington, Seattle, USA BACKGROUND: Our current understanding of sexual HIV transmission favors the initial uptake of virions by mucosal dendritic cells (DC), which then deliver HIV to CD4+ T cells. This sequential model has arisen mainly from studies with monocyte-derived DC and epidermal Langerhans cells (LC) rather than direct observations |
| 420 | The Distal Lower Genitourinary Tract as a Source of Seminal HIV. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 420) Coombs R, Deutsch L, Ross S, Dragavon J, Harb S, Motoshige A, Stensland L, Diem K, Hooton M, Collier A, Krieger J; Univ. of Washington, Seattle, USA BACKGROUND: Vasectomy does not affect the seminal shedding of HIV-1, suggesting that the distal male genitourinary (GU) tract is the major source of virus in semen. To investigate potential distal GU tract sources of HIV-1 we conducted extensive sampling of seropositive men who shed HIV-1 in their semen. METHODS: Semen |
| 421 | HIV-1 Cervicovaginal Reservoirs in the Era of HAART. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 421) Nunnari G, Kulkosky J, Sullivan J, Xu Y, Cavert W, Nyirjesy P, Frank I, Pomerantz RJ; Ctr. for Human Virology and Biodefense, Thomas Jefferson Univ., Philadelphia, PA, USA BACKGROUND: The aim of the study was to evaluate the role played by the cervical and vaginal tract in HIV-1 infected women on stable HAART, as a possible viral reservoir. METHODS: We enrolled 12 HIV-1-infected women on virally suppressive HAART (blood plasma HIV-1 RNA levels below 50 copies/mL) in this study. Cervicova |
| 422 | The Presence of Extracellular Virion-associated HIV-RNA in Lymphoid Tissue Reflects Local Productive Infection: A Detailed Analysis of Lymphatic HIV Transcription Patterns in vivo. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 422) Fischer M, Joos B, Wong JK, Hirschel B, Opravil M, Weber R, Guenthard HF; Univ. Hosp. Zurich, Switzerland BACKGROUND: To characterize transcription patterns indicative of ongoing or residual HIV-1 replication in patients with high level HIV-replication, suppressed viremia on HAART or limited replication early after structured treatment interruption, extracellular HIV-particles and intracellular viral RNAs were quantitated |
| 423 | Expression of Latent HAART-persistent HIV-1 Induced by Novel Cellular Activating Agents: Molecularly Interrogating HIV-1 Reservoirs. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 423) Pomerantz R, Sullivan J, Xu Y, Souder E, Hamer D, Kulkosky J; Thomas Jefferson Univ., Philadelphia, PA, USA and 2NCI, NIH, DHHS, Bethesda, MD, USA BACKGROUND: The novel anti-tumor promoting phorbol ester, prostratin, was evaluated for its ability to induce the expression of latent, HAART-persistent HIV-1 from specific sub-sets of patients peripheral blood cells. METHODS: These studies were performed relative to the use of other cellular activating agents, such as |
| 424 | Purging HIV-1 Viral Reservoirs: The Role of IL-7. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 424) Wang FX, Xu Y, Sullivan J, Fisher J, Souder E, Acheampong E, Argyris E, Frank I, Kulkosky J, Pomerantz RJ, Nunnari G; Ctr. for Human Virology and Biodefense, Thomas Jefferson Univ., Philadelphia, PA, USA and 2Univ. of Pennsylvania, Philadelphia, USA BACKGROUND: IL-7 is a cytokine produced by stromal and dendritic cells that is involved in the differentiation, survival and homeostasis of T-cells. In HIV-1-seropositive patients, serum levels of IL-7 are strongly correlated with CD4+ T-cell loss and increased HIV-1 viral load. Moreover, IL-7 is able to induce HIV-1 r |
| 425 | Actinomycin D and IL-6 Synergistically Stimulate HIV-1 Replication in a Latently Infected Cell Line U1 through Activating MRP8. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 425) Liu Y, Lempicki RA, Lane HC, Imamichi T; SAIC-Frederick, Inc., MD, USA and 2NIAID, NIH, DHHS, Bethesda, MD, USA BACKGROUND: Actinomycin D (Act D) is one of the most studied DNA-binding ligands. It functions as a potent antibiotic and antitumor agent. We previously reported that Act D enhanced HIV-1 replication in MT-2, but not MT-4, PBMC or Jurkat cells. In this study, we investigated the synergistic effect of Act D and IL-6 on |
| 426 | CD14lo/CD16hi Monocytes are More Permissive to HIV-1 Infection in vitro and May Selectively Harbour HIV-1 in Patients on HAART. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 426) Ellery P, Sonza C, Paukovics G, Cameron PU, Solomom A, Lewin R, Crowe SM; Macfarlane Burnet Inst. for Med. Res. and Publ. Hlth., Melbourne, Australia BACKGROUND: HIV-1 has been shown to persist in a number of cell types despite effective HAART. Previously, our laboratory has shown infectious HIV-1 may be readily recovered from monocytes of patients on HAART with undetectable VL. As less than 1% of monocytes harbor HIV, we hypothesize that there is a subset of monocy |
| 427 | Quantitation of Rare HIV-1 Integration Events in PBMC from HIV-1-infected Individuals Using Repetitive Sampling Techniques. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 427) Yu J, Swiggard WJ, Theodosopoulos T, O'Doherty U; Univ. of Pennsylvania, Philadelphia, USA and 2Drexel Univ., Philadelphia, PA, USA BACKGROUND: The frequency of latent reservoirs and integrated viral DNA within resting CD4+ T cells appear to be relatively constant in patients in the presence and absence of effective HAART. The limiting dilution co-culture assay is considered the gold standard to measure the frequency of reservoir cells, but it is t |
| 428 | Neutralizing Antibody Responses in Subtype-C-infected Heterosexual Seroconvertors in Zambia are Surprisingly High Titer. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 428) Decker J, Bibollet-Ruche F, Kasolo F, Musonda R, Allen S, Hahn BH, Shaw G, Hunter E, Derdeyn C; Howard Hughes Med. Inst., Birmingham, AL, USA BACKGROUND: We recently demonstrated that viruses pseudotyped with Env derived from heterosexual Zambian subjects newly infected with subtype C HIV-1 were unexpectedly sensitive to neutralization by plasma from the infecting partner and contained compact, glycan-restricted envelope glycoproteins. To determine the capac |
| 429 | Selective Transmission of Maternal HIV Neutralization Escape Variants: A Molecular Analysis. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 429) Dickover R, Garratty E, Yusim K, Miller C, Korber BT, Bryson Y; David Geffen Sch. of Med., Univ. of California, Los Angeles, USA and 2Los Alamos Natl. Labs, NM, USA BACKGROUND: Several reports have indicated that most cases of perinatal HIV infection are associated with transmission of a single maternal variant suggesting the presence of selective pressures during gestation and at the time of delivery. The role of maternal autologous neutralizing antibody as a selective factor in |
| 430 | Mannose-binding Lectin Binds and Opsonizes HIV and Prevents DC-SIGN-mediated Trans-infection, but Does Not Effectively Neutralize Virus. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 430) Ji X, Ying H, Hart M, Gupta K, Saifuddin M, Spear G; Rush Univ., Chicago, IL, USA BACKGROUND: Mannose binding lectin (MBL) is a soluble lectin in plasma that functions as a pathogen recognition molecule in innate immunity. Since MBL binds to HIV gp120, we investigated the anti-HIV activity of MBL. METHODS: To determine if primary isolates (PI) of HIV bind to MBL, virus was incubated in MBL-coated mi |
| 431 | Antibody Neutralization Escape Mediated by Point Mutations in the Intracytoplasmic Domain of HIV-1 GP41. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 431) Montelaro RC, Kalia V, Sarkar S, Gupta P; Univ. of Pittsburgh, PA, USA BACKGROUND: The persistence of HIV-1 infection in the presence of robust host immunity has been associated in part with variation of viral envelope proteins leading to antigenic variation and escape from neutralizing antibodies. Previous studies of natural neutralization escape mutants have focused predominantly on gp1 |
| 432 | Qualitative Properties of Antibody Binding Do Not Correlate with Neutralization of SIV. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 432) Cole KS, Steckbeck JD, Orlov I, Miller KA, Bruno J, Werkman JR, Polansky ND, Lin G, Hoxie JA, Montelaro RC; Univ. of Pittsburgh, PA, USA BACKGROUND: Despite a robust antibody response early after infection with HIV-1 or SIV, only a small proportion of antibodies elicited in vivo are capable of effectively neutralizing virus as measured in vitro. One hypothesis is that neutralization sensitivity is related to the density of envelope spikes on the virion, |
| 433 | A Strategy for Eliciting High-titer Cross-reactive Neutralizing Antibodies to Caprine Arthritis Encephalitis Virus Surface Glycoprotein SU. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 433) Trujillo J, Gonzalez M, Kumpula N, Hotzel K, Cheevers W; Washington State Univ., Pullman, USA BACKGROUND: Lentivirus vaccine development is hindered by the difficulty of eliciting high titer heterologous neutralizing antibodies. Recognition of immunodominant linear non-neutralizing or type specific neutralization epitopes is hypothesized to result in poor recognition of conformational neutralization epitopes. W |
| 434 | phiHIV-1 Infection of Human Monocyte-derived Macrophages Inhibits Granulocyte-macrophage Colony Stimulating Factor Signalling. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 434) Warby T, Crowe S, Jaworowski A; Macfarlane Burnet Inst. for Med. Res. and Publ. Hlth., Melbourne, Australia and 2Univ. of Queensland, Brisbane, Australia BACKGROUND: The function of mononuclear phagocytes is disrupted in HIV-1-infected patients contributing to a susceptibility to opportunistic infections characteristic of AIDS. granulocyte-macrophage colony stimulating factor (GM-CSF) is a growth factor which stimulates effector functions of phagocytes, e.g., phagocytos |
| 435 | HIV-1 Induced Cytokines Increase CCR5 Expression in FTOC. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 435) Choudhary S, Kimbrell K, Colasanti J, Ziogas A, Kwa D, Schuitemaker H, Camerini D; Univ. of California, Irvine, USA BACKGROUND: R5 HIV-1 strains persist throughout infection and are the only type of HIV-1 found in approximately half of AIDS patients. However, only about 5 to 25 % of mature T cells and 1 to 5% of thymocytes express detectable levels of CCR5. This creates a paradox, R5 HIV-1 clones can deplete nearly all CD4+ thymocyt |
| 436 | Differential Effects of TNF-alpha on HIV-1 Expression; Implication for Viral Evolution. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 436) Valentin A, Morrow M, Yarchoan R, Pavlakis GN; NCI at Frederick, NIH, DHHS, MD, MD USA and 2NCI, NIH, DHHS, Bethesda, MD, USA BACKGROUND: Cytokines, such as IL-4, and gammaIFN, can influence the levels of both HIV-1 and CCR5 expression on primary lymphocytes. Tumor necrosis factor alpha (TNFalpha) induces nuclear translocation of the transcriptional factor NFkappaB leading to increased activity from the HIV-1 LTR and stimulation of viral expr |
| 437 | HIV gp120 Induced TNF-alpha Production from Primary Human Macrophages: PI3 Kinase and MAPK Dependence. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 437) Lee CH, Tomkowicz B, Yi Y, Collman RG; Univ. of Pennsylvania Sch. of Med., Philadelphia, USA BACKGROUND: Interactions between HIV-1 and target cells through CD4 and the chemokine receptors, CCR5 or CXCR4, induce several cellular responses that can be dissociated from productive infection. In this study we investigated the signaling pathway elicited by HIV-1 envelope (Env) protein gp120 in human primary monocyt |
| 438 | Effects of the Proteasome Inhibitor PS-341 on Tumor Growth in HTLV-1 Tax Transgenic Mice and Tax Tumor Transplants. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 438) Kaushik R, Mitra-Kaushik S, Harding JC, Ratner L; St Louis, MO, USA BACKGROUND: The oncoprotein Tax from the Human T-cell Leukemia Virus type-1 is the major mediator of viral pathogenesis in infected individuals. Expression of Tax under the regulation of the granzyme B promoter in transgenic mice results in a lymphoproliferative disorder with features resembling adult T cell leukemia-l |
| 439 | HIV-1 Viremia Prevents the Establishment of IL-2-Producing HIV-Specific Memory CD4+T Cells Endowed with Proliferative Capacity. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 439) Younes SA, Yassine-Diab B, Dumont AR, Boulassal R, Grossman Z, Routy JP, Sekaly RP; Montreal Univ., Canada Backround: Memory CD4+ T-cell responses are associated with control of disease progression in chronic viral infections. Since HIV infects CD4+ T cells, it is thought that appropriate immune responses are impaired. However, little is known regarding the mechanisms of CD4+ T cells depletion in HIV infection and discrepan |
| 440 | Sustained Decline in T-cell Activation in Patients under Successful HAART is Associated with Higher CD4+ T Cell Gains. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 440) Benito JM, Lopez M, Lozano S, Martinez P, Gonzalez-Lahoz J, Soriano V; Madrid, Spain BACKGROUND: In patients on HAART, expression of CD38 on CD8 T cells has been proposed as a marker of residual viral replication. Herein, we have analyzed the evolution of CD38 on CD8 T cells in a group of HAART-treated patients showing complete viral supression during a follow-up period of 24 months. METHODS: Levels of |
| 441 | Loss of CD127 Defines a Generalized Memory T-cell Dysfunction in HIV-infected Patients. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 441) Cervasi B, Paiardini M, Albrecht H, Muthukumar A, Sodora D, Altman JD, Feinberg MB, Silvestri G; Emory Univ., Atlanta, GA, USA and 2Univ. of Texas Southwestern Med. Ctr., Dallas, USA BACKGROUND: HIV infection is associated with a complex T-cell dysfunction that is related to both the virus-mediated killing of infected CD4+ T cells and the state of chronic, generalized activation of the immune system. We investigated the pathogenesis of this dysfunction by analysing the expression of the interleukin |
| 442 | Increasing Viral Diversity Following Primary HIV-1 Infection Reflects Positive Selection but Does Not Correlate to Changes in CD4 Counts or Viral Loads. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 442) Smith D, Hightower G, Pond SK, Ignacio C, Richman D, Daar E, Little S, Frost S; Univ. of California, San Diego, USA BACKGROUND: Most new HIV infections occur through monoclonal or oligoclonal events. During the course of HIV infection, the host s immune response drives an increase in the diversity of the viral population. The nature and clinical consequences of this increasing diversity remains unclear. METHODS: We retrospectively a |
| 443 | Preferential Apoptosis of HIV-1 Specific CD4+ T cells. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 443) Yue E, Kovacs C, Dimayuga R, Parks P, Ostrowski M; Univ. of Toronto, Canada BACKGROUND: In contrast to other viral infections such as CMV , the frequencies of circulating HIV-1 specific CD4+ T cells in peripheral blood are quantitatively diminished in the majority of HIV-1 infected individuals. One mechanism for this quantitative defect has been preferential infection of HIV-1-specific CD4+ T |
| 444 | Chronic Immune Activation Leads to T Cell Depletion: a Mouse Model for HIV Pathogenesis. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 444) Hazenberg M, Galkina S, Chkhenkeli G, Stoddart C, McCune M; Gladstone Inst. of Virology and Immunology, San Francisco, CA, USA BACKGROUND: The level of immune activation is a strong predictor of HIV disease progression, suggesting that continuous, HIV-induced activation of the immune system may play a role in T cell depletion. We tested the hypothesis that persistent, non-HIV-1 related activation of the immune system by itself can lead to naiv |
| 445 | HIV M-tropic Envelope Signaling Through the CCR5 Co-receptor Induces Apoptosis in T Cells. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 445) Villasis-Keever A, Vlahakis S, Gomez T, Paya C; Mayo Clinic, Rochester, MN, USA BACKGROUND: Progressive depletion of CD4+ and CD8+ T cells is a hallmark of HIV type 1 (HIV-1) infection. Viral envelope protein gp120/41 enhances the rate of apoptosis in CD4+ T cells. The HIV-1 env protein signals through the primary viral receptor, CD4, and its co-receptor, either CCR5 or CXCR4. In this study, we ha |
| 446 | env, Not nef, Is a Cytopathic Determinant of R5 AIDS HIV-1. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 446) Olivieri K, Scoggins R, Taylor JR Jr, Matthews A, Charnauskas D, Brodrick B, Chmura M, Rekosh D, Hammarskjold ML, Camerini D; Univ. of Virginia, Charlottesville, USA and 2Univ. of California, Irvine, USA BACKGROUND: AIDS-associated R5 HIV-1 (R5-AIDS HIV-1) biological clones have greater cytopathic effects (CPE) for CD4+ thymocytes and replicate to higher levels than pre-AIDS R5 biological clones in SCID mice bearing human thymus/liver grafts (SCID-hu mice). We evaluated the env and nef genes as cytopathic determinants |
| 447 | High Prevalence of R77Q Vpr Mutation in Long-term Non-progressors from an Italian Cohort of HIV-1-infected Patients. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 447) Mologni D, Zanone-Poma B, Gianelli E, Monolo G, Quinzan G, Milazzo L, Galli M, Riva A; Univ. of Milan, Italy BACKGROUND: HIV-1 Viral Protein R (vpr) is a 96 amino acids soluble protein that is expressed late during viral replication. Vpr is rapidly lost among HIV-1 isolates, while it is maintained in most HIV-1-infected patients, suggesting that it may be important for the in vivo biology of HIV-1. A recent report showed that |
| 448 | Activation of CD4+ Naïve Lymphocytes Decreases Expression of P-glycoprotein, but Not Multi-drug Resistance Associated Protein 4. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 448) De Pasquale MP, Allos T, Sutton L, Shintani A, Grill SM, Unutmaz D, D'Aquila RT; Vanderbilt Univ. Med. Ctr., Nashville, TN, USA BACKGROUND: P-glycoprotein (Pgp) is relevant for HIV pathogenesis because it can modulate intracellular PI concentrations, as well as cell infectability. We observed earlier that Pgp RNA levels were significantly reduced in circulating lymphocytes from HIV infected, antiretroviral naïve patients compared with uninfecte |
| 449 | Chemokine Coreceptor Control of TRAIL Induced Apoptosis by gp120 and SDF-1. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 449) Lum JJ, Nie Z, Weaver J, Lee H, Lynch DH, Badley AD; Univ. of Ottawa, Ontario, Canada BACKGROUND: The mechanism and regulation of TRAIL-induced apoptosis of HIV-infected cells is unknown. HIV Tat has been shown to modulate TRAIL/TRAIL receptor function, however the contribution of other HIV proteins is unknown. Therefore, we examined the effect of gp120 ligation of CD4 and chemokine co-receptors on TRAI |
| 450 | CD4+ T-cell Depletion in AIDS: Synergy between Non-infectious HIV-1 and Other Viruses Induces Selective Apoptosis via a TRAIL/TRAIL Receptor-dependent Mechanism. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 450) Herbeuval JP, Boasso A, Lifson JD, Yagita H, Shearer GM; NCI, NIH, DHHS, CI, Bethesda, MD, USA BACKGROUND: Non-infectious HIV-1 virions have been suggested to induce anergy and/or apoptosis in T cells. We used HIV-1 viruses rendered noninfectious by chemical treatment with aldrithiol-2 (AT-2 HIV-1 virus), which preserves functional envelope glycoproteins, to evaluate this question, and to assess the possible con |
| 451 | Perturbation of CD4+ T Cell Subsets during HIV-1 Infection. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 451) Grill S, Leelawong M, Richter K, Motsinger A, Hulgan T, Nagata K, Haas DW, Unutmaz D; Vanderbilt Univ. Med. Sch., Nashville, TN, USA and 2BML Inc., Res. and Devt. Ctr., Matoba, Kawagoe Saitama, Japan BACKGROUND: Chronic HIV-1 infection is characterized by lymphocyte hyperactivation and a gradual loss of naïve and memory CD4+ T cells. Human memory T cells are comprised of functionally and phenotypically distinct subsets. T cells that are CD45RO+/CCR7+ (central memory) have lower effector functions and are long-lived |
| 452 | Specific Depletion of CD27+B220- Memory B Cells in HIV Infection. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 452) Morrow M, Valentin A, Yarchoan R, Pavlakis GN; NCI at Frederick, NIH, DHHS, MD, MD USA and 2NCI, NIH, DHHS, Bethesda, MD, USA BACKGROUND: In addition to CD4+ T cell depletion, HIV-1 infection is characterized by changes in humoral immunity including hypergammaglobulinemia, polyclonal B cell activation and loss of circulating memory B lymphocytes. Expression of B220, a CD45 isoform originally identified as a murine pan-B cell marker, has recen |
| 453 | Low-level Antigenic Exposure Differentially Affects T-cell Activation and HIV-specific T-cell Response. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 453) Karlsson A, Younger S, Martin J, Grossman Z, Sinclair E, Hunt P, Hagos E, Wrin T, Petropolous C, Nixon D, Deeks S; Gladstone Inst. of Virology and Immunology, Univ. of California, San Francisco, USA BACKGROUND: HIV replication, HIV-specific T cell responses and T cell activation each contribute to disease outcome in untreated individuals. The interaction of these factors is not well understood, particularly in subjects receiving antiretroviral therapy. We hypothesized that a viremic range might exist in which the |
| 454 | HIV-1 Superinfection in a Rapid Disease Progressor: Rapid Replacement of the Initial Strain with the Superinfecting Virus by Natural Selection Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 454 Gottlieb G, Nickle D, Jensen M, Wong K, Kaslow R, Margolick J, Mullins J; Univ. of Washington, Seattle, USA BACKGROUND: Superinfection with a second strain of HIV-1 has important implications for understanding HIV transmission and for vaccine development. However, the frequency and pathogenic consequences of superinfection are largely unknown, as are the underlying host-virus interactions associated with HIV-1 superinfection |
| 455 | HIV-1 Recombination in Individuals with Recent Infection. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 455) Palmer S, Kearney M, Maldarelli F, Achaz G, Rock D, Planta A, Mellors J, Daar E, Coffin J; HIV Drug Resistance Prgm., NCI, NIH, DHHS, Frederick, MD, USA BACKGROUND: Recombination is important in the evolution of HIV-1 with approximately 10% of circulating HIV-1 being intersubtype recombinants. This observation implies that intrasubtype recombination is also likely to be frequent, albeit more difficult to detect. To study the frequency of HIV-1 recombination in vivo we |
| 456 | Dynamics of HIV-1 Recombination in its Natural Target Cells. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 456) Levy DN, Aldrovandi G, Shaw GM; Univ. of Alabama at Birmingham, USA BACKGROUND: Quantitative models of HIV-1 dynamics, diversification and escape need to account for the contribution of genetic recombination but have yet to do so. Important aspects of HIV-1 recombination remain poorly defined, including the propensity of HIV-1 to productively infect cells with more than one virion (a n |
| 457 | No Setpoint in HIV RNA Level; a Model of Joint Natural History of CD4 Count and HIV RNA Level after Seroconversion. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 457) Geskus R, Meyer L, Hubert BJ, Schuitemaker H, Berkhout B, Rouzioux C, Theodorou I, Delfraissy JF, Prins M, Coutinho R; Municipal Hlth. Svc., Amsterdam, The Netherlands BACKGROUND: According to the setpoint theory, HIV-1 RNA level remains at stable levels from shortly after infection until a few years before the development of AIDS. Over the last years, this theory has been critcised. We reconsidered this theory by modelling the joint development of CD4 and HIV-1 RNA level from HIV in |
| 458 | The Effects of Gonococcal, Chlamydial and Non-specific Urethritis on Seminal Plasma HIV-1 RNA Loads in the United Kingdom. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 458) Sadiq ST, Taylor S, Copas AJ, Bennett J, Drake SM, Kaye S, Kirk S, Pillay D, Weller IV; Royal Free and Univ. Coll. Med. Sch., London, UK BACKGROUND: Little is known of the impact of sexually transmitted infections (STI) on seminal HIV-1 shedding in antiretroviral naïve individuals within the developed world. Conversely in sub-Saharan Africa, urethritis has been associated with increased genital shedding of HIV-1, with median differences of over 100,000 |
| 459 | Comparison of HIV-1 pol and env Sequences of Blood, CSF, Brain, and Spleen Isolates, a Longitudinal Study. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 459) Caragounis EC, Svennerholm B, Nordborg C, Westergren S, Lindh M, Hagberg L, Gisslen M; Goteborg Univ., Sweden BACKGROUND: To address the issue of independent HIV-1 evolution within the central nervous system (CNS) and study the origin of HIV-RNA extracted from the cerebrospinal fluid (CSF). METHODS: Longitudinally derived paired blood and CSF samples and autopsy samples from ventricular CSF, frontal cortex, parietal sub-cortex |
| 460 | Phenotype Analysis of HIV-1 Envelopes Amplified from Brain and Lymph Node Tissue of AIDS Patients with Neuropathology Identifies Envelopes with an Enhanced Tropism and Fusigenicity for Macrophages. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 460) Peters P, Bhattacharya J, Hibbitts S, Dittmar M, Simmons G, Bell J, Simmonds P, Clapham P; Univ. of Massachusetts Med. Sch., Worcester, USA BACKGROUND: HIV-1 replication in the brain results in AIDS dementia complex in about 30% of AIDS patients. The mechanisms that lead to neuropathogenesis are unclear. Also it is not known whether neurotropic or neurovirulent HIV-1 variants are involved. Others reported HIV-1 isolates with enhanced tropism and fusigenici |
| 461 | HIV-1 Nef Sequence Diversity Is Associated with Reduced Neural Stem Cell Survival. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 461) Marle G, McArthur J, Rourke S, Power C; Univ. of Calgary, Alberta, Canada BACKGROUND: HIV-1 infection causes neurodegeneration through toxic effects mediated by HIV-1 proteins such as Nef. While most studies have focused on neuron and astrocyte survival, the effects of HIV infection on neural stem cell survival have not been investigated to date. Our objective was to examine the effects of H |
| 462 | Role of HIV-1 Vpr-binding Brain Protein (VBP) in Neuropathogenesis of HIV-1-associated Dementia. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 462) Miles M, Janket M, Majumder B, Schafer E, Achim C, Ayyavoo V; Univ. of Pittsburgh, PA, USA BACKGROUND: HIV-associated dementia (HAD) is the most common cause of dementia in AIDS patients worldwide and is considered one of the independent risk factors for death due to AIDS. During early infection, HIV-1 enters the Central Nervous System (CNS) and resides in macrophages/microglia. Although HIV replicates in th |
| 463 | Nociceptive Neruons Are Particularly Vulnerable to gp120 Neurotoxicity Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 463 S Keswani*, M Polley, and A Hoke Johns Hopkins Hosp., Baltimore, MD, USA BACKGROUND: Pedal pain dominates the symptomatology of HIV-associated sensory neuropathy, which is now recognized as the most common neurological complication of HIV infection. The neuropathic pain is often so severe that it interferes with walking and sleep. Little attention has so far been devoted to exploring the pa |
| 464 | Induction of Neuron Death by HIV-1 Tat Expression in Astrocytes. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 464) Zhou B, He J; Indiana Univ. Sch. of Med., Walther Cancer Inst., Indianapolis, USA BACKGROUND: One of the pathological hallmarks in HIV-associated dementia is neuron death. Nevertheless, neurons are not directly infected by HIV-1. Thus, indirect and soluble factors produced by HIV-infected microglia/macrophages and astrocytes have been proposed for HIV-induced neuropathologies. Among them is HIV-1 Ta |
| 465 | Peripheral Nerve-derived HIV-1 is Both CXCR4 and CCR5 Dependent and Reduces Neurite Outgrowth in Dorsal Root Ganglia Cultures. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 465) Jones G, Zhu Y, McArthur JC, Pardo C, Silva C, Keppler O, Power C; Univ. of Calgary, Alberta, Canada BACKGROUND: The most common form of peripheral neuropathy seen in HIV/AIDS is distal sensory polyneuropathy (DSP), which is defined by both spontaneous and evoked pain, paresthesiae, and hypesthesia together with both large and small caliber axonal loss following a dying back pattern of degeneration. To date, little i |
| 466 | HIV-1 Gag Host Cell Interactions During Budding and Assembly in Macrophages/Microglia. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 466) Vos R, Albright A, Ryzhova E, Gonzalez-Scarano F; Univ. of Pennsylvania, Philadelphia, USA BACKGROUND: We have previously reported a model for low-level, long-lived infection of microglia/brain macrophages under non-activating conditions (no serum or cytokines). We determined that these cells could be infected with little to no viral output compared to the productive infection of activated microglia; whereas |
| 467 | Antiviral Effect of HIV-1-specific siRNA against Targets Conserved in Select Neurotropic Strain. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 467) Dave R, Pomerantz R; Ctr. for Human Virology and Biodefense, Thomas Jefferson Univ., Philadelphia, PA, USA BACKGROUND: The antiviral effect of HIV-1-specific siRNA has been demonstrated by several research groups. However, the targets that were selected in previous studies are not conserved in several neurotropic HIV-1 strains. Previously described studies, including the one we present, will ultimately enable us to evaluate |
| 468 | Sustained Antiretroviral Activity of Indinavir Nanosuspensions in Primary Monocyte-derived Macrophages. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 468) Limoges J, Kadiu I, Morin D, Chaubal M, Werling J, Rabinow B, Gendelman HE; Univ. of Nebraska Med. Ctr., Omaha, USA and 2Baxter Healthcare Corp., Round Lake, IL, USA BACKGROUND: Highly active anti-retroviral therapy (HAART) has diminished the incidence and severity of HIV-1 associated dementia (HAD). However, a significant disease prevalence, poor nervous system penetration of many antiretroviral medicines, viral back-mutation (from brain to blood) and a failure to eradicate reserv |
| 469 | HIV, Hepatitis C, and Methamphetamine Dependence Independently Worsen Neuropsychological Performance. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 469) Letendre S, Cherner M, Marquie-Beck J, Ellis R, Heaton R, Marcotte T, Harrington K, Gragg B, McCutchan J, Grant I; Univ. of California, San Diego, USA BACKGROUND: HIV, HCV, and Meth are each associated with central nervous system (CNS) complications. All 3 may injure the CNS by similar mechanisms, such as macrophage activation, oxidative stress, and direct neuronal injury. The objective of this study was to determine if HIV, HCV, and Meth are independently associated |
| 470 | Astrocyte-Tissue Inhibitor of Metalloproteinase-1 in HIV-1-associated Dementia: The Unexpected Neuronal Defender? Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 470) Ghorpade A, Deshpande M, Borgmann K, Persidsky R, Wu L, Gardner J, Dhar A, Holter S; Ctr. for Neurovirology and Neurodegenerative Disorders, Univ. of Nebraska Med. Ctr., Omaha, USA BACKGROUND: Astrocyte production of tissue inhibitor of metalloproteinase (TIMP)-1 plays an important role in central nervous system homeostasis and inflammatory diseases such as HIV-1-associated dementia . While originally discovered as an inhibitor of matrix metalloproteinases (MMP), recently, TIMP-1 has emerged as a |
| 471 | Erythropoietin Is Neuroprotective in in vitro Models of HIV Neuropathy. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 471) Keswani S, Polley M, Leitz G, Hoke A; Johns Hopkins Hosp., Baltimore, MD, USA and 2Ortho Biotech Products, Raritan, NJ, USA BACKGROUND: HIV-associated sensory neuropathy is now recognized as the most common neurological complication of HIV infection, symptomatically affecting one third of AIDS patients. HIV-associated sensory neuropathy includes 2 phenotypically identical neuropathies: distal symmetrical polyneuropathy, associated with HIV |
| 472 | Relationship between Alzheimer's Disease and AIDS Dementia Complex Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 472 B Brew*, and L Pemberton St. Vincent's Hosp., Sydney, Australia BACKGROUND: Alzheimer’s disease (AD) is associated with the following factors: increased age, hyperlipidemia, and chronic brain inflammation. HIV infected patients treated with Highly Active Antiretroviral Therapy (HAART) also often have such abnormalities. AD is currently thought related to excess amyloid beta product |
| 473 | Neuronal Apoptosis Is mediated by IP-10 Over-expression in Simian Human Immunodeficiency Virus Encephalitis. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 473) Buch S, Sui Y, Potula R, Narayan O, Nath A, Kolson D; Kansas Univ. Med. Ctr., Kansas City, USA BACKGROUND: Inflammatory mediators play a crucial role in the pathophysiology of several neurodegenerative diseases including AIDS Dementia Complex. METHODS: In the present study we identified a link between CXCL10 overexpression in the brain and HIV dementia and demonstrated the presence of the chemokine CXCL10 and it |
| 474 | HIV-1 Interaction with Human Mannose Receptor on Astrocytes Induces Protein Dephosphorylation and Production of Matrix Metalloproteinase 2. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 474) Lopez-Herrera A, Liu Y, He JJ; Indiana Univ. Sch. of Med., Indianapolis, USA BACKGROUND: A number of studies have shown that astrocytes are susceptible to HIV-1 infection, although CD4 expression is not detected on these cells. We have recently demonstrated that human mannose receptor is directly involved in CD4-independent HIV-1 infection of astrocytes. Despite a high binding affinity of HIV-1 |
| 475 | The Receptor Tyrosine Kinase, RON, Negatively Regulates HIV-1 Transcription and is Decreased in HIV-associated Demented Patients. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 475) Kalantari P, Lee E, Correll P, Power C, Henderson A; Penn State, Univ. Park, USA and 2Univ. of Calgary, Alberta, Canada BACKGROUND: Inappropriate recruitment of macrophages to brain and aberrant activity of microglia contribute to HIV-associated central nervous system (CNS) diseases. The mechanisms that initiate and maintain inflammation following HIV-1 infection in the CNS have not been well studied. Furthermore, it is not understood w |
| 476 | TRAIL Induce Apoptosis and Production of Glutamate in HIV-1-infected Macrophage: Linkage to HIV-1-associated Dementia. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 476) Huang Y, Zhao J, Ryan LA, Lopez A, Peng H, Herek S, Zheng J; Univ. of Nebraska Med. Ctr., Omaha, USA BACKGROUND: Pro-inflammatory factors and neurotoxins, produced by mononuclear phagocytes as a consequence of viral infection, can induce neuronal injury during HIV-1-associated dementia . Tumor necrosis factor related apoptosis inducing ligand (TRAIL), is a type II integral membrane protein, which interacts with multip |
| 477 | Pathogenesis of Progressive Multifocal Leukoencephalopathy: Global Modulation of Host Gene Expression. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 477) Verma S, Bui T, Frisque RJ, Yanagihara R, Nerurkar VR; Univ. of Hawaii at Manoa, Honolulu, USA and 2Pennsylvania State Univ, Univ. Park, USA BACKGROUND: JC virus (JCV), the etiological agent of the fatal demyelinating disease PML, infects oligodendrocytes. Once a rare disease, PML occurs in 3-5% of AIDS patients. The restricted tropism of JCV makes pathogenesis-related studies challenging. Because of the difficulties in cultivating JCV, most pathogenesis st |
| 478 | The Monocyte Chemotactic Protein-1 -2578 G Allele Is Associated with Elevated MCP-1 Concentrations in Cerebrospinal. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 478) Letendre S, Marquie-Beck J, Singh K, Spector S, Almeida S, Zimmerman J, Lazzaretto D, Ellis R; Univ. of California, San Diego, USA BACKGROUND: MCP-1 is an important co-factor in HIV neuropathogenesis. The data that support this include elevated MCP-1 expression in the CSF of subjects with HIV-associated dementia (HAD), and a 4.5-fold increased risk of HAD associated with the MCP-1 -2578G allele. This allele is also associated with higher MCP-1 con |
| 479 | Development of in vitro Models for Studies on HIV Neuropathogenesis. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 479) Wang J, Gabuzda D; Dana-Farber Cancer Inst., Boston, MA, USA BACKGROUND: HIV infection of the central nervous system frequently causes neurological disorders. To understand mechanisms that underlie neurodegeneration in HIV infection, novel cell culture models were developed. METHODS: Primary human microglia, astrocytes, and neurons were purified from human brain cell cultures ba |
| 480 | Measures of Human Lymphocyte Transmigration into Brain in a Murine Model of HIV-1 Encephalitis. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 480) Mosley RL, Zelivyanskaya ML, Dou H, Lewis TB, Poluektova LY, Uberti M, Mellon M, Nelson A, Boska MD, Gendelman HE; Univ. of Nebraska Med. Ctr., Omaha, USA BACKGROUND: For much of the course of HIV-1 infection, viral replication is highly restricted within the nervous system. Neurological disease occurs with significant immune suppression and ongoing viral production. Anti-HIV adaptive immunity serves as a major regulator of viral infection in brain. Nonetheless, the dyna |
| 481 | Effects of Statins on the Transmigration of Monocytes and T Cells across the Blood Brain Barrier. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 481) Mengistu A, Acheampong E, Nunnari G, Argyris E, Kalayeh M, Williams KJ, Pomerantz RJ, Mukhtar M; Thomas Jefferson Univ., Philadelphia, PA, USA BACKGROUND: HIV-1 penetration of the brain in AIDS-associated dementia is an important event in the onset and progression of the disease. The infiltration of HIV-1 infected monocytes and macrophages into the central nervous system (CNS) is one of the indicators of the disease. However, the mechanisms by which monocytes |
| 482 | The Peripheral Benzodiazepine Receptor Can Be Used to Quantify Macrophages In SIV Encephalitis. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 482) Venneti S, Wiley CA; Univ. of Pittsburgh Sch. of Med., PA, USA BACKGROUND: HIV infection and SIV infection in macaques leads to profound neurological disease primarily mediated by infiltration of the brain with infected and activated macrophages in approximately 25% of infected individuals. Our objective is to quantify activated macrophages in post mortem brain tissue. Several stu |
| 483 | Human Progenitor Derived Astrocytes Phagocytized HIV-1 through Mannose Receptor. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 483) Trujillo JR, Jensen P, Maric D, Major EO; NINDS, NIH, DHHS, Bethesda, MD, USA BACKGROUND: Over the last decade, much progress has been made in the identification of cellular protein receptors for HIV-1. However, little is known about the carbohydrate receptors that might also bind HIV-1. We have shown that the macrophage/microglia mannose receptor supports HIV-I binding and entry. In this report |
| 484 | HIV-1 Enters Primary Human Brain Microvascular Endothelial Cells by a Mechanism Involving Cell-Surface Proteoglycans Independent of Lipid Rafts. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 484) Argyris EG, Acheampong E, Nunnari G, Mukhtar M, Williams KJ, Pomerantz RJ; Thomas Jefferson Univ., Philadelphia, PA, USA BACKGROUND: Recent studies have reported a crucial role for cholesterol-enriched membrane lipid rafts and cell-associated heparan sulfate proteoglycans (HSPG) in HIV-1 entry into permissive cells. In this study we examined the role of these cell-surface moieties in HIV-1 entry into primary human brain microvascular end |
| 485 | Molecular Analysis of Blood and Cerebrospinal Fluid Treponema pallidum in Neuroinvasion Compared to Neurosyphilis in HIV-infected Individuals. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 485) Marra CM, Bashiri H, Centurion A, Mittler J, Lukehart SA; Univ. of Washington, Seattle, USA BACKGROUND: Neuroinvasion by Treponema pallidum is common in early syphilis; neurosyphilis, with CSF abnormalities, is less common. The tprK gene in T. pallidum is a single-copy gene that is heterogeneous within and among T. pallidum strains. Organisms within a strain are polyclonal as defined by their tprK sequences, |
| 486 | Predominantly Concordant CCR5 Chemokine Receptor Utilization in CSF and Plasma in a Survey Sample of HIV-infected Subjects. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 486) Spudich S, Nilsson A, Onstott K, Huang W, Whitcomb J, Price RW; San Francisco, CA, USA and 2South San Francisco, CA, USA BACKGROUND: Chemokine receptors (CCR) serve as co-receptors for entry of HIV-1 into host cells, are important for determination of infected cell spectrum, and may, along with their ligands, play a more direct role in HIV neurotoxicity. CCR utilization, most commonly involving CCR5 or CXCR4, associates by clinical plasm |
| 487 | HIV-1-induced Synaptic Dysfunction and Its Attenuation by Memantine in a Murine Model of HIV Encephalitis. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 487) Anderson ER, Poluektova L, Gendelman HE, Xiong H; Univ. of Nebraska Med. Ctr., Omaha, USA BACKGROUND: It has been shown by several groups that HIV-1-associated neurotoxicity could be attenuated by NMDA receptor antagonists in vitro. To unravel the mechanism for HIV-1-induced neurotoxicity in vivo and to explore therapeutic potential for HIV-1 disease, we studied how chaunges in synaptic transmission and pla |
| 488 | Neuroprotective Effects of Non-immunosuppressive Immunophilin Ligands in Antiretroviral Toxic Neuropathy is Mediated by hsp70 Pathway. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 488) Schneider J, Keswani S, Polley M, Liang H, Hoke A; Johns Hopkins Univ., Baltimore, MD, USA BACKGROUND: Peripheral neuropathy is the most common neurological complication of HIV infection affecting quality of life and effective use of HAART regimens. Antiretroviral toxic neuropathy is caused by direct mitochondrial toxicity by some of the NRTIs and recently we have shown that an immunophilin ligand, FK506, wa |
| 489 | HAART Modified Risk of HIV Dementia Associated to Increasing Age Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 489 P Lorenzini1, D Larussa1, A Cingolani2, I Uccella1, M Bongiovanni3, M L Giancola1, S Bossolasco4, F Moretti5, V Tozzi1, P Zannoni6, C F Perno1, A Ammassari2, A d'Arminio Monforte3, P Cinque4, A Antinori*1, and Italian Registry Investigative Neuro AIDS (IRINA) BACKGROUND: Epidemiologic studies, in pre-HAART era suggested that age may be a risk factor for HIV dementia . Even though increased survival of treated patients has been associated with an increased development of chronic diseases, the effect of HAART on risk of cognitive impairment associated to increasing age has no |
| 490 | Novel High-concentration Capsaicin Patch for the Treatment of Painful HIV-aAssociated Distal Symmetrical Polyneuropathy: Results of an Open Label Trial Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 490 D Simpson*1, S Brown2, J Sampson3, L Estanislao1, C Vilahu4, S Ramanathan4, J Jermano4, and T von Stein4 1Mt. Sinai Med. Ctr., New York, NY; 2AIDS Res. Alliance, West Hollywood, CA, USA; 3The Res. & Education Group, Portland, OR; and 4NeurogesX, Inc., San Carlos, CA BACKGROUND: Activation by capsaicin of vanilloid receptors (TRPV1) expressed in dermal and epidermal nociceptive sensory nerve fibers results in burning pain sensations followed by functional inactivation of these nociceptors. Low-concentration capsaicin creams are used to treat various neuropathic pain conditions, but |
| 491 | Efavirenz Suppress the Rate of Viral Replication in Human Brain Tissue Infected with Zidovudine-resistant HIV. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 491) Kandanearatchi A, Vyakarnam A, Everall IP; Inst. of Psychiatry, Kings Coll., London, UK and Rayne Inst., Kings Coll., London, UK BACKGROUND: HIV neurocognitive disorder results in neurodegeneration and rising viral burden in brain and CSF. Clinical studies indicate antiretrovirals improves cognitive impairment, however which agents ameliorate brain damage is not known. Also, at present a number of drug resistant viral strains have emerged. Due t |
| 492 | Lithium Improves HIV-associated Neurocognitive Impairment. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 492) Letendre S, Woods S, Ellis R, Atkinson J, Brande G, Durelle J, Grant I; Univ. of California, San Diego, USA BACKGROUND: Lithium may protect neurons by several mechanisms, including modulation of Na+/K+ ion channels and 2) proteins associated with inflammation and apoptosis. The primary objective of this pilot study was to identify the effects of low-dose lithium on the NP performance of HIV-infected subjects with baseline ne |
| 493 | NARC007: Clinical Validation of the AACTG NeuroScreen Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 493 R Ellis*1, K Robertson2, L Moo3, D Clifford4, Y Yang5, C Yiannoutsos6, and S Evans5 1Univ. of California, San Diego, USA; 2Univ. of North Carolina at Chapel Hill, USA; 3Johns Hopkins Univ., Baltimore, MD, USA; 4Washington Univ., St. Louis, MO, USA; 5Harvard Sch. of Publ. Hlth., Boston, MA, USA; and 6Indiana Univ. Sch. of Med., Indianapolis, USA BACKGROUND: An important aim of AACTG studies A5001 (ALLRT) and A362 is to assess the impact of highly active combination antiretroviral therapies (HAART) on neurologic disease in HIV. To address this objective, the NeuroScreen, comprising brief assessments of neuropsychological (NP) function and distal sensory polyneu |
| 494 | Broad-spectrum Micronutrient Supplementation in HIV-infected Patients with Dideoxynucleoside-related Peripheral Neuropathy: A Prospective, Double Blind, Placebo-controlled Trial Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 494 J Kaiser*1, J Ondercin2, G Santos3, G Leoung4, S Brown5, M Mass6, and M Baum7 1Univ. of California, San Francisco, USA; 2Jonathan Lax Treatment Ctr., Philadelphia, PA, USA; 3Betances Hlth. Ctr., New York, NY, USA; 4HIVCare, St. Francis Mem. Hosp., San Francisco, CA, USA; 5AIDS Res. Alliance, West Hollywood, CA, USA; 6California Pacific Med. Ctr., San Francisco, USA; and 7Florida Intl. Univ., Miami, USA BACKGROUND: Dideoxynucleoside-related neuropathy affects upwards of 20% of patients taking stavudine or didanosine . A possible mechanism is mitochondrial toxicity due to free oxygen species toxicity. Based on this hypothesis, we tested a potent antioxidant for |
| 495 | Potentially Preventive Effect of Didanosine against HIV Encephalopathy. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 495) Martin IP, Milon MP, Drogoul MP, Enel P, Gastaut JA, Vion-Dury J; CISIH, Hosp. Ste Marguerite, Marseille, France BACKGROUND: Although incidence of HIV -encephalopathy has declined since the introduction of HAART, many patients currently still present cognitive impairement. Proton magnetic resonance spectroscopy (MRS) is a well recognized method to evaluate early brain metabolism impairement in HIV infected patients. METHODS: Retr |
| 496 | The Effect of Smoked Marijuana on Chronic Neuropathic and Experimentally Induced Pain in HIV Neuropathy: Results of an Open-label Pilot Study Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 496 C Jay*, S Shade, H Vizoso, H Reda, K Petersen, M Rowbotham, and D Abrams Univ. of California, San Francisco, USA BACKGROUND: Painful polyneuropathy remains a significant clinicial problem in patients with HIV infection. Preclinical studies suggest that cannabinoids may be effective in neuropathic pain syndromes. METHODS: Open-label pilot inpatient study conducted over 9 days in the General Clinical Research Center. Eligible subje |
| 497 | Response of HIV-associated Sensory Neuropathies to Early Detection and Treatment Manipulation Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 497 C Cherry*1,2,3, J McArthur4, L Lal1, P Hauer4, and S Wesselingh1,2,3 1Macfarlane Burnet Inst. for Med. Res. and Publ. Hlth., Melbourne, Australia; 2Monash Univ., Melbourne, Australia; 3Alfred Hosp., Melbourne, Australia; and 4Johns Hopkins Univ., Baltimore, MD, USA BACKGROUND: Sensory neuropathies (SN) are the commonest neurological complications of HIV and are associated with significant morbidity. Both distal sensory polyneuropathy (DSP, due to HIV) and antiretroviral toxic neuropathy (ATN, attributed to mitochondrial dysfunction from NRTI) are described. We hypothesize that ap |
| 498 | Improved Cognitive Function in Immune Reconstituted Advanced AIDS Patients Is Associated with Maintenance of HIV Suppression Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 498 A McCutchan*1, J Wu2, P Williams2, K Robertson3, R Ellis1, S Koletar4, and J Currier5 1Univ. of California, San Diego, USA; 2Harvard Sch. of Publ. Hlth., Boston, MA, USA; 3Univ. of North Carolina at Chapel Hill, USA; 4Ohio State Univ., Columbus, USA; and 5Univ. of California, Los Angeles, USA BACKGROUND: Continuing HIV-induced brain damage during otherwise successful HAART is plausible because of the limited CNS penetration by some antiretroviral drugs and is supported by epidemiological and magnetic resonance spectroscopic studies. We hypothesized that neuropsychological impairment might progress despite s |
| 499 | Presence of Nucleotide Excision Resistance Mutations in Cerebrospinal Fluid Is Associated with Reduced Prevalence of HIV-Related Brain Lesions. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 499) Pierotti C, Nebuloni M, Bestetti A, Presi S, Terreni MR, Sala SE, Sala ST, Carrera P, Lazzarin A, Vago L, Cinque P; San Raffaele Hosp., Milan, Italy and 2Luigi Sacco Hosp., Milan, Italy BACKGROUND: Highly active antiretroviral therapy, but also simpler anti-HIV treatment regimens, including zidovudine ( AZT ) monotherapy or dual nucleoside reverse transcriptase inhibitor (NRTI) combinations, have been associated with a reduced prevalence of both HIV- |
| 500 | MCP-1 and HIV Viral Load Dynamics in Cerebrospinal Fluid and Plasma are linked in AIDS Patients Changing Antiretroviral Therapy. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 500) Almeida S, Letendre S, Zimmerman J, Lazzaretto D, Ellis R; UFPR, Curitiba, Parana, Brazil and 2Univ. of California, San Diego, USA BACKGROUND: Monocyte chemoattractant protein (MCP)-1 is a chemokine that is particularly important in HIV neuropathogenesis, in part because it mediates macrophage migration into the brain. To date, dynamic changes in MCP-1 expression and HIV replication over time have been studied in cell culture and animal models, bu |
| 501 | Neurological Functioning and CNS Penetrating Antiretroviral Regimens Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 501 K Robertson*, W Robertson, S Ford, A Harp, and C Hall Univ. of North Carolina at Chapel Hill, USA BACKGROUND: Antiretrovirals have poor penetration into the CNS, leading to speculation that virus may become sequestered in the CNS,increasing the propensity for neurological disease. It is not known whether regimens with higher CNS penetration may provide more protection from neurological disease. METHODS: Data from 4 |
| 502 | Diabetes and Cognitive Functioning Among HIV Seropositive Patients. The Hawaii Aging with HIV Cohort. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 502) Valcour V, Shikuma C, Shiramizu B, Grove J, Watters M, Grove J, Watters M, Poff P, Selnes O, Sacktor N; Univ. of Hawaii, Honolulu, USA and 2Johns Hopkins Univ., Baltimore, MD, USA BACKGROUND: Metabolic complications including diabetes (DM) and insulin resistance have been conclusively associated with HIV infection. The addition of HAART has had further deleterious effects on metabolic risk factors in this already vulnerable population, particularly among older patients. Correlation to neurocogni |
| 503 | CD14+/CD16+ Monocytes Are Enriched in Cerebrospinal Fluid Compared to Blood of HIV-1-infected Subjects, Especially during Successful ART. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 503) Neuenburg JK, Furlan S, Nilsson A, Price RW; Gladstone Inst. of Virology and Immunology, Univ. of California, San Francisco, USA and 2Univ. of California, San Francisco, USA BACKGROUND: Activated CD14+/CD16+ monocytes likely play a critical role in the pathogenesis of HIV-1-related brain disease and have been found in brains of HIV-1 infected subjects with and without clinical dementia . These monocytes/macrophages are located in the perivascular area of the brain and derive from blood-bor |
| 504 | Early Brainstem Damage Is Predictive of Poor Survival in HIV-infected Patients with Progressive Multifocal Leukoencephalopathy. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 504) Gasnault J, Herve MG, Rahoiljaon J, Delfraissy JF, Taoufik Y; Hosp. Univ. de Bicetre, Le Kremlin Bicetre, France and 2INSERM E0109, Le Kremlin Bicetre, France BACKGROUND: About 50% of HIV+ patients with progressive multifocal leukoencephalopathy (PML) on HAART have poor prognosis and decease during the first months of PML. Brainstem damage may occur early in the course of PML and could be a worsening factor. METHODS: A monocenter observational study of consecutive patients w |
| 505 | Cerebrospinal Fluid HIV Concentration is Highly Associated with Blood CD8+ T Cell Activation and Antiretroviral Treatment Responses. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 505) Sinclair E, Ronquillo R, Bigos M, Nilsson A, Deeks S, Csajka C, Verotta D, Price R; Univ. of California, San Francisco, USA and 2Gladstone Inst. Virology and Immunology, San Francisco, CA, USA BACKGROUND: HIV RNA is frequently detected in the CSF, but its relationship to the concentration of HIV in plasma is highly variable. To examine factors contributing to CSF HIV levels, we performed a multivariate analysis of salient laboratory and clinical variables (including markers of T-cell activation in blood and |
| 506 | Macrophage Chemotactic Protein Levels in Cerebrospinal Fluid of Patients with AIDS-associated PML Treated with HAART Favorably Correlate with Patients Survival. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 506) Marzocchetti A, Cingolani A, Giambenedetto SD, Giancola ML, Antinori A, De Luca A; Inst. di Clinica delle Malattie Infettive, Catholic Univ. of Sacro Cuore, Rome, Italy and 2Inst. Natl. delle Malattie Infettive, IRCCS "Lazzaro Spallanzani'', Rome, Italy BACKGROUND: Despite improved survival with HAART, prognosis of AIDS-associated progressive multifocal leukoencephalopathy remains poor; cases of progressive multifocal leukoencephalopathy have been discribed on HAART, some showing features of immune reconstitution syndrome. Others have shown a beneficial effect of infl |
| 507 | Neurocognitive Impairment and Survival in HIV-Positive Patients Treated with HAART: Results from an Urban Observational Cohort Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 507 V Tozzi*, P Balestra, D Serraino, R Bellagamba, A Corpolongo, C Vlassi, P Piselli, U Visco-Comandini, M E Quartuccio, D Larussa, L Pucillo, N Petrosillo, G Ippolito, A Antinori, and P Narciso INMI L. Spallanzani, Rome, Italy BACKGROUND: Before HAART introduction, HIV-associated neurocognitive impairment was recognized as an independent risk factor for death. Our aim was to determine whether neurocognitive impairment represents a negative prognostic factor for mortality also in patients treated with HAART. METHODS: Since 1996, we have been |
| 508 | Antiretroviral Drugs Penetrating CSF Do Not Influence Neurocognitive Performance in HIV-1 -infected Patients Responders to HAART Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 508 A Antinori*, P Balestra, M L Giancola, M E Quartuccio, D Larussa, P Lorenzini, F Baldini, A Corpolongo, R Bellagamba, and V Tozzi INMI Lazzaro Spallanzani IRCCS, Rome, Italy BACKGROUND: HAART has resulted in increased survival of HIV infected patients and in a decreased incidence of HIV Dementia, but the impact of treatment with CSF penetrating drugs on HIV associated neurocognitive impairment in routine practice deserves more attention. METHODS: Cross-sectional study on HIV-infected patie |
| 509 | Beneficial Effects of IL-2 and GM-CSF Immunotherapy in Immune Restoration Disease and on HIV-1-Specific T-Cell Responses after Antiretroviral Therapy. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 509) Imami N, Pires A, Nelson M, Pozniak A, Fisher M, Gazzard B, Gotch F; Imperial Coll., London, UK and 2Chelsea and Westminster Hosp., London, UK BACKGROUND: In late-stage HIV-1 disease, antiretroviral therapy (ART) although controlling viral replication and allowing some immune reconstitution, does not allow restoration of HIV-1-specific T-cell responses. In some cases, lack of response to other pathogens allows for emergence of severe immune reconstitution dis |
| 510 | Interleukin-2 Prior to Stopping Effective Antiretroviral TherapyProlongs Time Off Treatment: Initial Results of a Pilot Study Utilizing CD4++ T-cell Count <350 cells/mm3 as the Threshold for Restarting ART (ACTG A5102). Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 510 Henry K, Tebas P, Cherng D, Schmitz J, Katzenstein D, Valdez H, Jahen N, Vargas M, Myers L, Sahner D, Powderly W, the Adult AIDS Clinical Trials Group and A5102 Team; Univ. of Minnesota, Minneapolis, USA BACKGROUND: Both ART and interleukin-2 ( IL-2 ) generally increase CD4+ T-cell counts in HIV-infected individuals. We evaluated the use of IL-2 in an intermittent antiretroviral therapy strategy that initiates and stops antiretroviral therapy at specific CD4 thresholds. ACTG 5102 was designed to evaluate the effect of |
| 511 | IL-7/IL-7 Receptor System Regulation Following IL-2 Immunotherapy in HIV-infected Patients. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 511) Marchetti G, Meroni L, Molteni C, Taskaris G, Gazzola L, Galli M, Clerici M, Moroni M, Franzetti F, Gori A; Inst. of Infectious Diseases and Tropical Med., Univ. of Milan, Italy and 2Univ. of Milan, Italy BACKGROUND: Interleukin-2 ( IL-2 ) and interleukin-7 (IL-7) are the most intriguing molecules in immune-based HIV infection treatment. An in vitro IL-2/IL-7 cross-talk secondary to IL-2-driven IL-7 receptor-alpha-chain (IL-7Ralpha) down-modulation, potentially blocking IL-7-signalling has been described. We aimed at in |
| 512 | IL-15 Treatment of SIV-infected Non-human Primates. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 512) Petrovas C, Mueller YM, Bojczuk P, Dimitriou ID, Beer B, Silvera P, Villinger F, Cairns JS, Lewis MG, Katsikis PD; Drexel Univ. Coll. of Med., Philadelphia, PA, USA BACKGROUND: We have recently shown that in vitro IL-15 inhibits apoptosis, enhances survival and augments the effector function of HIV-specific CD8+ T cells. In the present pilot study we examine the effect of in vivo IL-15 treatment on virological and immunological parameters in SIV-infected non-human primates. METHOD |
| 513 | Filgrastim Stimulates HIV-1 Replication in Monocytoid Cells. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 513) Rapaport R, McLean C, Campbell TB; Univ. of Colorado Hlth. Sci. Ctr., Denver, USA BACKGROUND: Recombinant granulocyte colony stimulating factor (rG-CSF or filgrastim) is used to treat neutropenic complications of human immunodeficiency virus type 1 (HIV-1) and occasionally to mobilize hematopoietic stem cells (HSC) in HIV-1-infected persons. In a previous study, filgrastim activated replication of H |
| 514 | Cyclooxygenase-2 Inhibitors Induce T Cell Subset Changes in Patients on Highly Active Antiretroviral Treatment and with Persistent Viremia. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 514) Kvale D, Ormaasen V, Kran AM, Froland S, Tasken K; Ulleval Univ. Hosp., Oslo, Norway BACKGROUND: We have previously characterized how elevated cAMP can abolish T cell receptor (TCR)-mediated activation, and found that HIV patients have elevated cAMP/PKA-mediated inhibition of TCR reactivity. CI reduce PGE2 and can thereby indirectly reduce T cell cAMP. A recent 14 d pilot study suggested that CI improv |
| 515 | Long-term Evolution without Antiretroviral Therapy of Chronic HIV-1-infected Patients with Good Virological Response to Cycles of Structured Treatment Interruption. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 515) Florence E, Garcia F, Plana M, Fumero E, Castro P, Cruceta A, Gil C, Arnedo M, Pumarola T, Gallart T, Gatell JM; Hosp. Clin.-IDIBAPS, Barcelona Univ., Spain BACKGROUND: Our objectives were to assess the long-term evolution (>2 years) of CHI patients included in structured treatment interruption protocols who complied with predefined criteria of good virological evolution and to investigate the factors associated with this good response. METHODS: We recruited 60 CHI with a |
| 516 | Gene Therapy of HIV Infection by Transduced Autologous CD4+ T Cells Inhibiting Viral Entry. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 516) Lunzen J, Brandenburg G, Baum C, Kuehlcke K, Koopman G, Alexandrov A, Stahmer I, Stellbrink HJ, Laer D; Univ. Hosp. of Eppendorf, Hamburg, Germany BACKGROUND: HAART has significantly improved the survival of HIV-infected pts. However, the duration of response may be limited by the development of drug-resistant HIV variants and long-term toxicities indicating the need for innovative strategies. Our objective was to develop an effective gene therapy for HIV infecti |
| 517 | HIV-Blocking Fully Human Antibodies against CCR5 Generated by 2-Hybrid System. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 517) Hua SB, Pauling M, Erichsen D, Lin YH, Tran A, Zheng J, Zhu L; Genetastix Corp., San Jose, CA, USA and 2Univ. of Nebraska Med. Ctr., Omaha, USA BACKGROUND: HIV-1 induces virus-cell membrane fusion to gain entry into target cells. In addition to the receptor CD4, the CC chemokine receptor CCR5 is a principal HIV-1 coreceptor that plays a dominant role in disease transmission and in the early course of infection. CCR5 is a member of GPCR (G-protein coupled recep |
| 518 | Final Results of A Phase I Study of a Therapeutic Vaccine Using Autologous Dendritic Cells Primed with Autologous Virus in Patients with Chronic HIV Infection and CD4 T Cells above 400/Mm3. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 518) Garcia F, Lejeune M, Climent N, Gil C, Alcami J, Morente V, Alos L, Florence E, Libois A, Pereira A, Miro JM, Pumarola T, Plana M, Gatell JM, Gallart T; Hosp. Clin.-IDIBAPS, Barcelona Univ., Spain and 2Inst. Carlos III, Madrid. BACKGROUND: To assess the virologic and HIV-specific immune responses after vaccination with HIV-pulsed DC in successfully treated chronic HIV-infected patients. METHODS: Autologous MD-DC from patients (median 2x106 cells), obtained from a 60-ml venous blood, were pulsed with autologous heat inactivated HIV-1 (mean 4x1 |
| 519 | Analysis of Nef-specific T-cells, Viral Rebound and Autologous Viral Sequences during Structured Treatment Interruption after Therapeutic Vaccination with a MVA-BN-Nef Vaccine in HIV-1-infected Patients on HAART. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 519) Harrer E, Bauerle M, Ferstl B, Chaplin P, Petzold B, Bergmann S, Hamacher M, Eismann K, Kalden JR, Harrer T; Univ. Hosp. Erlangen, Germany and 2Bavarian-Nordic, Martinsried, Germany BACKGROUND: Structured treatment interruptions after therapeutic vaccination can provide important information about the efficacy of vaccines and the role of CTL. In this study we interrupted HAART after vaccination with a MVA-BN-Nef vector (Modified Vaccinia Virus Ankara-Bavarian Nordic) and we correlated the CTL resp |
| 520 | Use of Solvent Treated SIV to Induce/Augment SIV-specific CD4+ and CD8+ T Cell Memory Responses in Mice: A Model for a New Therapeutic Vaccination Strategy against HIV Infection. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 520) Ansari A, Villinger F, Hildreth JE, Mayne A, Maltais JB; Emory Univ. Sch. of Med., Atlanta, GA, USA BACKGROUND: Novel strategies need to be identified and studied for the immune reconstitution of HIV-infected humans to supplement HAART. Current chemotherapeutic strategies, while highly effective, are not without significant side effects, and are associated with increased risk of selection for multi-drug resistant HIV |
| 521 | BAY 50-4798, an IL-2 Selective Agonist, Is Associated with Lower Levels of Cytokine Production than Aldesleukin. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 521) Steppan S, Eckart M, Greve J, Cassell D; Biotechnology Res., Bayer Corp., Berkeley, CA, USA BACKGROUND: Combination therapy with highly active antiretroviral therapy (HAART) and aldesleukin (Proleukin) produces sustained increases in CD4+ T-cell counts and augments the immune system more effectively than HAART alone. However, treatment with aldesleukin is associated with toxicity, which may be due to the elic |
| 522 | Human Pharmacokinetic Evaluation of the IL-4/13 Trap: a Novel Immunomodulatory Agent for the Treatment of HIV Disease. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 522) Parsey M, Fauci G, Dunn J, Marks C, Skop E, Stahl N, Furfine E; Regeneron Pharm., Tarrytown, NY, USA BACKGROUND: A strong CTL response to HIV infection is considered required for the ultimate control of HIV disease. Most subjects chronically infected with HIV have a limited HIV-selective CTL response. IL-4 and IL-13 are potent attenuators of a CTL response. A novel biologic agent, the IL-4/13 Trap, blocks IL-4 and IL- |
| 523 | Dynamics of T Cells Homeostasis Induced by Tucaresol. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 523) Gazzola L, Marchetti G, Bandera A, Trabattoni D, Molteni C, Meroni L, Thorborn D, Panebianco R, Moroni M, Franzetti F, Bray D, Clerici M, Gori A; Inst. of Infectious Diseases and Tropical Med., Univ. of Milan, Italy Background; Tucaresol is a Schiff base-forming immunomodulant which proved safe and effective in enhancing HIV-specific cytotoxic T-cell responses. We evaluated T-cell dynamics induced in vivo by tucaresol in different populations of HIV+ patients treated with and without HAART. METHODS: We studied 17 HIV+ patients enr |
| 524 | Immediate Immunity against HIV Infection and Adjuvant Activity of gamma delta T Lymphocytes by Aminobiphosphonate plus IL-2 Administration. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 524) Poccia F, Casetti R, Martino A, D'Offizi G, Horejsh D, Martini F; Natl. Inst. for Infectious Diseases "L.Spallanzani", Rome, Italy BACKGROUND: Human gdT cells carrying the Vg9Vd2TCR recognize non-peptidic antigens generated by abnormal metabolic routes during microbial infections and certain cancers. Vg9Vd2 T cell effectors are lacking in immunocompromised HIV-infected persons, suggesting that boosting gdT cell effectors could be clinically releva |
| 526 | Analysis of the Genotypes of Viruses Isolated from Patients after 10 Days Monotherapy with SPD754 Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 526 P Collins*1, L Shiveley2, C Anderson2, and R Bethell1 1Shire Biochem, Laval, Canada and 2Shire Pharm. Inc., Rockville, MD, USA BACKGROUND: SPD754 is a cytidine analogue with activity against HIV-1, including isolates resistant to other available NRTI. SPD754 has predictable pharmacokinetics and shows low potential for cytotoxicity and mitochondrial toxicity in vitro. Introduction of a new NRTI brings the risk of resistance. Phase 2 monotherapy |
| 527 | Safety Profile of SPD754 in Cynomolgus Monkeys Treated for 52 Weeks Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 527 C Locas*1, S Ching2, and S Damment3 1Shire Biochem, Laval, Canada; 2SVC Associates Inc., Laval, Canada; and 3Shire Pharm. Devt., Basingstoke, UK BACKGROUND: SPD754 is a cytidine analogue with activity against HIV-1, including isolates resistant to other available NRTI. SPD754 was well tolerated and highly effective as short-term monotherapy in HIV+ patients. In vitro cytotoxicity and mitochondrial tolerability studies indicate that the (-) enantiomer, SPD754, h |
| 528 | Diarylpyrimidines and Diaryltriazines Constitute a New Class of Highly Active Non-Nucleoside Reverse Transcriptase Inhibitors Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 528 Y Van Herrewege*1, J Michiels1, Z Kara1, K Andries2, M P de Béthune2, L Kestens1, P J Lewi3, P A J Janssen3, and G Vanham1 1Inst. of Tropical Med., Antwerp, Belgium; 2Tibotec, Mechelen, Belgium; and 3Janssen Pharmaceutica, Vosselaar, Belgium BACKGROUND: Co-cultures of monocyte-derived dendritic cells (MO-DC) and autologous CD4++ T cells represent the primary target cells during sexual HIV transmission. The antiviral and immune suppressive activity of a new class of non-nucleoside reverse transcriptase inhibitors (NN-RTI), Diarylpyrimidines (DAPYs) and diar |
| 529 | Kinetic and Thermodynamic Parameters for Binding of the Non-nucleoside Inhibitors GW678248 and GW695634 to Wild Type and 12 Mutants of HIV-1 Reverse Transcriptase Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 529 G Roberts*, D Porter, L Boone, J Chan, L Martin-Carpenter, P Gerondelis, S Short, and K Weaver GlaxoSmithKline, Research Triangle Park, NC, USA BACKGROUND: The NNRTI candidate GW695634, in phase I clinical development, is the prodrug of GW678248. Antiviral activity of the prodrug was examined. The interactions of GW695634 and GW678248 with HIV-1 reverse transcriptase (RT) were investigated by spectroscopic techniques. Inhibition of primer unblocking was also i |
| 530 | Characterization of a Novel Series of Nevirapine-like Next-Generation NNRTI with Broad Antiviral Potency Against NNRTI-resistant HIV Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 530 P R Bonneau*1, L Doyon1, J Duan1, B Simoneau1, C Yoakim1, R Déziel2, W Ogilvie3, L Bourgon1, M Garneau1, F Liard1, C Plouffe1, S Tremblay1, E Wardrop1, M Bös1, and M G Cordingley1 1Boehringer Ingelheim (Canada) Ltd., Res. and Devt., Laval, Canada; 2Methylgene, Montréal, Québec Canada; and 3Univ. of Ottawa, Ontario, Canada BACKGROUND: Non-nucleoside reverse transcriptase inhibitors (NNRTI) are potent components of combination antiretroviral therapies. However patients failing on an NNRTI-containing regimen most often exhibit broad cross-resistance to all members of the class leaving them with no further NNRTI options. A pre-requisite for |
| 531 | Novel Tricyclic Non-Nucleoside Reverse Transcriptase Inhibitors with Improved Resistance Profiles. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 531) Johnson B, Tarby C, Srivastava A, Bakthavatchalam R, Bacheler L, Diamond S, Jeffrey S, Klabe R, Cordova B, Garber S, Logue K, Erickson-Viitanen S, Trainor G, Rodgers J; Bristol-Myers Squibb Co., Princeton, NJ, USA and 2DuPont Pharm. Co.,, Wilmington, DE, USA BACKGROUND: NNRTI therapy has become a key component of HAART for the treatment of HIV infection. However, increasing resistance to currently marketed NNRTIs has been reported in clinical studies. The goal of this work was to identify agents that maintain potency against a range of clinically relevant mutated viruses w |
| 532 | SN1212/1461 a Novel Mutagenic Deoxyribonucleoside Analog with Activity against HIV. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 532) Harris K, Brabant B, Li L, Styrchak S, Gall A, Daifuku R; Koronis Pharm., Redmond, WA, USA Backgroune: It has been previously been shown that a MDRN can inhibit the growth of HIV following multiple passages in tissue culture. We have identified a substantially more potent MDRN, SN1212, that demonstrates antiviral activity in a single passage. SN1461 is an oral prodrug of SN1212. SN1212 is not a chain termina |
| 533 | TMC114/RTV Activity in Multiple PI-experienced Patients: Correlation of Baseline Genotype, Phenotype, Pharmacokinetics, and IQ with Antiviral Activity at Day 14 Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 533 M Peeters1, B Van Baelen1, S De Meyer1, M-P de Bethune1, H Muller1, R Hoetelmans1, E Lefebvre2, and E Delaporte* 1Tibotec, Mechelen, Belgium; 2Tibotec Inc., Yardley, PA, USA; and 3UR36, Inst of Res. and Devt., Montpellier, France BACKGROUND: TMC114 is a potent, next generation HIV protease inhibitor (PI) with in vitro antiviral activity against both wild-type and PI-resistant HIV-1. METHODS: In TMC114-C207, an open, randomized phase 2a study, patients on a virologically failing regimen received TMC114/RTV as a substitute for all PI or continued |
| 534 | Characterization of a Small Molecule HIV-1 Attachment Inhibitor BMS-488043: Virology, Resistance and Mechanism of Action Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 534 P F Lin*, H T Ho, Y F Gong, I Dicker, N Zhou, L Fan, B McAuliffe, B Kimmel, B Nowicka-Sans, T Wang, J Kadow, G Yamanaka, Z Lin, N Meanwell, and R Colonno Bristol-Myers Squibb Co., Wallingford, CT, USA BACKGROUND: High rates of therapeutic failure demands novel compounds aiming at new targets with superior pharmacokinetic/safety profiles. BMS-488043 (043) is an orally available HIV-1 Attachment inhibitor that was optimized through SAR to exhibit potent and selective antiviral activity along with superior pharmacokine |
| 535 | Safety, Tolerability, and Pharmacokinetics of a Novel, Small-Molecule HIV-1 Attachment Inhibitor, BMS-488043, after Single and Multiple Oral Doses in Healthy Subjects Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 535 G Hanna, J-H Yan*, W Fiske, T Masterson, D Zhang, and D Grasela Bristol-Myers Squibb Co., Princeton, NJ, USA BACKGROUND: BMS-488043 (043) is a novel, oral small-molecule inhibitor of HIV-1 entry that selectively prevents attachment of the exterior viral envelope protein gp120 to its cellular receptor CD4. A previously described member of the same class, BMS-378806, was well-tolerated but did not achieve target exposures after |
| 536 | Phase 1b Study of the Anti-CD4 Monoclonal Antibody TNX-355 in HIV-1-infected Subjects: Safety and Antiretroviral Activity of Multiple Doses. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 536) Jacobson JM, Kuritzkes DR, Godofsky E, DeJesus E, Lewis S, Jackson J, Frazier K, Fagan EA, Shanahan WR; Beth Israel Med. Ctr., New York, NY, USA BACKGROUND: TNX-355, a humanized IgG4 anti-CD4 domain 2 monoclonal antibodies, showed potent anti-HIV-1 activity in vitro and in a phase 1a single-dose study in HAART-experienced subjects (CROI, 2003). METHODS: TNX-355 was added as a single new drug to unchanged ART or none for =2 months in 22 HIV-1-infected subjects w |
| 537 | Control of HIV-1 Replication in the hu-PBL-SCID Mouse Model by an Anti-CCR5 Monoclonal Antibody. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 537) Franti M, Ramos L, Maloveste S, Geerdes D, Nagashima KA, Ketas TJ, Delgado K, Maddon PJ, Olson WC, Poignard P; Scripps Res. Inst., La Jolla, CA, USA BACKGROUND: The CC-chemokine receptor CCR5 is a promising target for HIV-1 entry inhibitors. We examined the therapeutic potential of the anti-CCR5 monoclonal antibody PRO140 in the hu-PBL-SCID mouse model of HIV-1 infection. METHODS: SCID-mice were reconstituted with PBMCs from a CCR5 wild-type donor and infected with |
| 538 | Reversible Predominance of CXCR4 Utilising Variants in a Non-Responsive Dual Tropic Patient Receiving the CCR5 Antagonist UK-427,857. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 538) Westby M, Whitcomb J, Huang W, James I, Abel S, Petropoulos C, Perros M, Ryst E; Pfizer Global Res. and Devt., Sandwich, UK and 2ViroLogic Inc., South San Francisco, CA, USA BACKGROUND: A concern in developing co-receptor antagonists as a novel class of HIV therapeutics is the possible emergence of X4 variants during treatment. Our objective was to perform a detailed analysis of a patient harboring virus with a dual-tropic phenotype, who was inadvertently enrolled in a phase 2a clinical st |
| 539 | in vitro Anti-HIV Activity Profile of AMD887, a Novel CCR5 Antagonist, in Combination with the CXCR4 Inhibitor AMD070. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 539) Schols D, Vermeire K, Hatse S, Princen K, Clercq ED, Calandra G, Fricker S, Nelson K, Labrecque J, Bogucki D, Zhou Y, Skerlj R, Bridger G; Rega Inst. for Med. Res., Leuven, Belgium and 2AnorMED Inc., Langley, Canada BACKGROUND: The antiviral efficacy of several CCR5 antagonists (e.g. SCH-C, UK427,857) (against R5 viruses) and a CXCR4 antagonist (e.g., AMD3100) (against X4 viruses) was demonstrated in clinical phase 2 studies. Here, we evaluated the in vitro anti-HIV activity of a novel CCR5 antagonist (AMD887) and AMD070, a recent |
| 540 | Determination of Binding Sites of a Unique CCR5 Inhibitor AK602 on Human CCR5. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 540) Maeda K, Ogata H, Harada S, Tojo Y, Miyakawa T, Nakata H, Takaoka Y, Shibayama S, Sagawa K, Daikichi F, Moravek J, Arnold E, Mitsuya H; Kumamoto Univ. Sch. of Med., Japan BACKGROUND: A novel spirodiketopiperazine derivative, AK602/ONO4128/GW873140 exerts potent activity against R5 HIV-1 in vitro. We characterized the CCR5 binding profile of AK602 and its interactions with HIV-1 gp120, CC-chemokines, and CCR5 in comparison with those of other previously published CCR5 inhibitors. METHODS |
| 541 | KRH-2731: An Orally Bioavailable CXCR4 Antagonist Is a Potent Inhibitor of HIV-1 Infection. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 541) Murakami T, Yoshida A, Tanaka R, Mitsuhashi S, Hirose K, Yanaka M, Yamamoto N, Tanaka Y; Univ. of the Ryukyus, Okinawa, Japan BACKGROUND: Chemokine receptors, CXCR4 and CCR5, which are used as coreceptors by HIV-1, are considered attractive targets for possible intervention of HIV-1 infection. We previously reported KRH-1636 as a duodenally absorbable CXCR4 antagonist and X4 HIV-1 inhibitor. Our continuous efforts to find more effective CXCR4 |
| 542 | Selective Ablation of HIV-infected Lymphocytes by Inhibitors of Hypusine Formation: The Mature Eukaryotic Translation Initiation Factor 5A Is Pivotal for Retroviral Suppression of Apoptosis. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 542) Hanauske-Abel HM, Palumbo P, Park MH, Wolff EC, Fernadez A, Garcia Z, Hardegen N, Popowicz AM, Cracchiolo BM, McLendon GL; New Jersey Med. Sch.-UMDNJ, Newark, USA BACKGROUND: Mature eukaryotic translation initiation factor 5A (eIF5A), involved in nucleocytoplasmic transport of certain mRNA, contains the functionally essential residue hypusine. The latter is formed by deoxyhypusine hydroxylase (DOHH), a 2-oxoacid utilizing non-heme iron dioxygenase whose catalysis follows the HAG |
| 543 | Anti-HIV Effects of Chloroquine: Inhibition of Viral Particle Glycosylation and Synergism with Protease Inhibitors. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 543) Savarino A, Lucia MB, Rastrelli E, Rutella S, Golotta C, Morra E, Tamburrini E, Boelaert JR, Sperber K, Cauda R; Catholic Univ. of S. Cuore, Rome, Italy BACKGROUND: Despite the diffusion of drug-resistant malaria, chloroquine (CQ) is at present the most widely diffused antimalarial in Africa. This drug exerts anti-HIV effects additive to those of NRTI by inhibiting viral particle maturation in the Golgi and also inhibits surface drug transporters such as the P-glycopro |
| 544 | Antiviral Effects of Mifepristone and its Analogs on HIV-1 Vpr-Induced Virus Replication. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 544) Schafer E, Wagner M, Ayyavoo V; Univ. of Pittsburgh, PA, USA BACKGROUND: Most HAART regimens eventually fail to provide complete and long-term suppression of virus replication due to the inability to fully clear virus replication in non-dividing cellular reservoirs. The HIV-1 viral protein R, Vpr, increases virus replication in T cells and is necessary for the infection of prima |
| 545 | Determinants of Activity, in vitro Metabolism and in vivo Disposition of the Novel Maturation Inhibitor PA-457. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 545) Martin DE, Smith P, Goila-Gaur R, Salzwedel K, Li F, Kilgore N, Reddick M, Matallana C, Castillo A, Zoumplis D, Allaway G, Freed E, Wild C; Panacos Pharm., Gaithersburg, MD, USA BACKGROUND: PA-457 is the lead drug candidate in a new class of antiretrovirals that inhibit HIV replication by disrupting virus maturation. PA-457 blocks a late step in Gag processing that results in defective core condensation and the release of non-infectious virus particles. Specifically, PA-457 disrupts the conver |
| 546 | Selective Killing of HIV Infected Cells by Small Molecule Cyclin Dependent Kinase Inhibitors. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 546) Hesselgesser J, Gibbs CS, Shibata R; Gilead Sci., Inc., Foster City, CA, USA BACKGROUND: During HAART the number of HIV-infected cells in vivo rapidly declines due to the short life span of activated/infected T-lymphocytes, killing by cytotoxic T-cells, and the intrinsic cytotoxicity of HIV. Nonetheless, even after several years of successful HAART substantial numbers of infected cells still re |
| 547 | Efficacy and Safety of Atazanavir with Ritonavir or Saquinavir vs Lopinavir/Ritonavir in Patients Who Have Experienced Virologic Failure on Multiple HAART Regimens: 48-Week Results from BMS A1424-045 Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 547 E DeJesus1, B Grinsztejn2, C Rodriguez3, L Nieto-Cisneros4, J Coco5, A Lazzarin6, K Lichtenstein7, M Johnson*8, A Rightmire9, S Sankoh10, and R Wilber10 1IDC Res. Initiative, Altamonte Springs, Florida, USA; 2Inst. de Pesquisa Clin. Evandro Chagas-Fiocruz, Rio de Janeiro, Brazil; 3Hosp. Argerich, Buenos Aires, Argentina; 4Hosp. Gabriel Mancera, IMSS Mexico, D.F., Mexico; 5Pendleton Memorial Methodist Hosp., New Orleans, LA, USA; 6S. Raffaele Hosp., Milan, Italy; 7Univ. of Colorado Hlth. Sci. Ctr., Denver, USA; 8Royal Free Hosp., London, UK; 9Bristol-Myers Squibb Co., Hopewell, NJ, USA; and 10Bristol-Myers Squibb Co., Wallingford, CT, USA BACKGROUND: Atazanavir (ATV) is a potent azapeptide PI with a pharmacokinetic profile allowing for once-daily dosing. ATV trough levels are boosted 5- to 8-fold by ritonavir (RTV) co-administration. The objectives of the study are to compare the efficacy and s |
| 548 | A Randomized Trial of 1 or 2 Protease Inhibitors in Combination with a Non-nucleoside Reverse Transcriptase Inhibitor and Background Therapy in Patients with Virologic Failure on an Initial Protease-inhibitor Containing Regimen. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 548) Kostman J, Grund B, Leduc R, Baxter J, Crane L; Univ. of Pennsylvania Hlth. System, Philadelphia, USA BACKGROUND: In CPCRA 057, investigators chose 1 of 2 treatment strategies, based on genotype and treatment experience, in patients (pts) with virologic failure on their first protease inhibitor (PI) containing regimen. This report describes the randomized comparison of 1 vs. 2 PIs in combination with a non-nucleoside r |
| 549 | Final Week 48 Analysis of a Phase 4, Randomised, Open-label, Multi-center Trial to Evaluate Safety and Efficacy of Continued Lamivudine Twice Daily Versus Discontinuation of Lamivudine in HIV-1-infected Adults with Virological Failure on Ongoing Combination Treatments Containing Lamivudine: The COLATE Trial Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 549 U Dragsted*1, Z Fox1, L Mathiesen2, C Katlama3, M Youle4, J Gerstoft5, J N Bruun6, and J D Lundgren for the COLATE trial group1 1Copenhagen HIV Prgm., Hvidovre Univ. Hosp., Denmark; 2Hvidovre Univ. Hosp., Copenhagen, Denmark; 3Hosp. de la Pitié- Salpêtriére, Paris, France; 4Royal Free Hosp., London, UK; 5Rigshospitalet, Copenhagen, Denmark; and 6Ullevål Univ. Hosp., Oslo, Norway BACKGROUND: Lamivudine ( 3TC ) is commonly used in HIV-1 treatment regimens both prior to and following virological failure. In vitro data suggest benefit of continuing 3TC after virological failure. The COLATE trial is the first randomised clinical assessment of this |
| 550 | Virologic Failure in Antiretroviral Therapy Naïve Patients Is Only Determined by Extreme Low Values of CD4+ Cells or High Values of HIV-1 RNA Concentration, Not by Choice of Treatment with Nevirapine or Efavirenz. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 550) Leth F, Andrews S, Grinsztjen B, Wilkins E, Lazanas M, Lange J, Montaner J; Intl. Antiviral Therapy Evaluation Ctr., Amsterdam, The Netherlands BACKGROUND: The 2NN study was the first large randomized trial to compare efficacy and safety of the two most widely used non-nucleoside reverse transcriptase inhibitors, nevirapine (NVP) and efavirenz (EFV). The present study looks in-depth at the influence of the |
| 551 | Analysis of Virologic Failure in a Clinical Trial of Abacavir Once Daily versus Twice Daily with Lamivudine and Efavirenz. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 551) Craig C, Stone C, Bonny T, Zhao H, Gordon D, Castillo S, Paes D; GlaxoSmithKline, Stevenage, UK BACKGROUND: Once daily regimens may simplify antiretroviral therapy. Study CNA30021was a randomized, double-blind, multicenter, international study to examine the efficacy of ABC once daily vs ABC twice daily. METHODS: Plasma from subjects with virological failure (failure to achieve plasma HIV-1 RNA |
| 552 | Emergence of Resistance Mutations During Intermittent HAART. Rate, Predicting Factors, and Effect on Virologic Response. Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 552 Palmisano L, Giuliano M, Bucciardini R, Galluzzo CM, Andreotti M, Fragola V, Arcieri R, Amici R, Weimer L, Germinario E, Pirillo MF, Vella S, and the Italian ISS PART Clinical Centers; Inst. Superiore di Sanita, Rome, Italy BACKGROUND: The emergence of resistance mutations is one of the major safety concerns of intermittent HAART in chronic HIV infection. We monitored the occurrence of mutations in the ISS PART study, an ongoing randomized multicenter clinical trial comparing continuous (arm A) versus intermittent (arm B) HAART in 273 sub |
| 553 | Factors Associated with Virologic Failure and Their Impact on Treatment Outcomes: An Analysis of Virologic Failure in ACTG 388. Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 553 Ribaudo H, Downey G, Fischl M, Feinberg J, Erice A, Collier A; Harvard Sch. of Publ. Hlth., Boston, MA, USA BACKGROUND: Despite the success of HAART regimens in antiretroviral naïve study subjects, virologic failure is seen in 10% to 30% of subjects over 3 years of follow-up. Understanding factors that influence the risk of virologic failure is important to improve virologic outcome in these subjects. METHODS: We analyzed ba |
| 554 | Time to Triple Drug Class Failure after Initiation of HAART. Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 554 Mocroft A, Ledergerber B, Viard JP, Staszewski S, Murphy M, Chiesi A, Horban A, Hansen AB, Phillips AN, Lundgren JD, the EuroSIDA study group; Royal Free and Univ. Coll. Med. Sch., London, UK BACKGROUND: After exposure to the three main classes of antiretrovirals treatment options in patients with HIV may be limited due to difficulties in maintaining undetectable levels of viraemia, decreasing CD4 counts and clinical disease progression. We sought to describe the incidence of and time to virologic triple dr |
| 555 | Factors Associated with Improved Survival among Heavily Antiretroviral Treatment Experienced Patients in the HIV Outpatient Study. Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 555 Palella FJ Jr, Chmiel JS, Kirby KA, Moorman AC, Holmberg SD, the HOPS investigators; Northwestern Univ., Chicago, IL, USA and 2CDC, Atlanta, GA, USA BACKGROUND AND METHODS: To evaluate factors associated with improved survival among HIV-infected persons with extensive antiretroviral treatment (ART) experience we analyzed data from 1116 participants in the HIV Outpatient Study (HOPS) seen from January 1, 1994 to June 30, 2003, with >/=4 years of ART, >/=6 months wit |
| 556 | Response to HAART in HIV-infected Persons Older than 50 Years. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 556) Moore R, Keruly J, Gebo K, Lucas G, Chaisson R; Johns Hopkins Univ., Baltimore, MD. USA BACKGROUND: Several previous studies suggest that HIV-infected persons over 50 may respond less well to HAART due to poorer immune response and other factors. We sought to compare response to HAART in patients =50 vs |
| 557 | Low Baseline CD4 T-cell Count and Higher Age Predict Poor CD4 T-cell Recovery in Treated HIV-1 Infected Individuals Suppressing HIV-1 RNA to Levels <1000 copies/mL for 5 Years. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 557) Kaufmann G, Furrer H, Perrin L, Ungsedhapand C, Opravil M, Egger M, Cavassini M, Vernazza P, Bernasconi E, Rickenbach M, Hirschel B, Battegay M; Univ. Hosp. Basel, Switzerland BACKGROUND: Antiretroviral therapy (ART) for HIV-1 infection results in variable recovery of CD4 T-lymphocytes. Few studies have explored the characteristics and predictors of poor CD4 T-cell responses to long-term ART. METHODS: Longitudinal CD4 T-cell count was analyzed in 326 participants of the Swiss HIV Cohort Stud |
| 558 | Improvement in Virologic, Immunologic, and Clinical Outcomes in Clinical Practice from 1996 to 2002 Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th: (abstract No. 558 R Moore*, J Keruly, K Gebo, and G Lucas Johns Hopkins Univ., Baltimore, MD. USA Background: Early studies indicated that only ~50% of patients receiving HAART in clinical practice had virologic suppression. HAART utilization has evolved since 1996. We sought to determine how virologic and other outcomes of HAART use have changed in clinical practice since 1996. Methods: We assessed the virologic, |
| 559 | The Use of Observational Databases to Compare Anti-retroviral Effectiveness. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 559) Keiser P, Nassar N, Yazdani B, Armas L, Moreno S; Univ. of Texas Southwestern Med. Ctr., Dallas, USA and 2Parkland Hlth. and Hosp. System, Dallas, TX, USA BACKGROUND: Use of computerized observational databases to compare anti-retroviral medications has not been fully validated. Concordance of response between patients in 3 observational databases and 3 randomized clinical trials has been demonstrated, but that study compared treatment strategies (i.e. HAART vs dual ther |
| 560 | Effect of Race on the Response to Highly-Active Antiretroviral Therapy. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 560) Anastos K, Schneider M; Montefiore Med. Ctr., Bronx, NY, USA BACKGROUND: Occurrence of AIDS-defining illness and death, and longitudinal changes in HIV-1 RNA and CD4+ cell counts following initiation of highly active antiretroviral therapy (HAART) among different racial groups have not been well described. METHODS: In 937 HIV-infected participants initiating HAART in the Women s |
| 561 | Hemoglobin as a Prognostic Factor for AIDS-defining Illness and Survival with the Use of HAART Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 561 Moore R, Keruly J; Johns Hopkins Univ., Baltimore, MD. USA BACKGROUND: The hemoglobin (Hg) level was consistently found to be associated with advanced HIV disease (both AIDS-defining illness and mortality) in multiple studies prior to the use of HAART, and in several studies in patients receiving HAART. We sought to determine its significance as a prognostic factor compared to |
| 562 | Impact of an Adherence Clinic on Behavioral Outcomes and Virologic Response: Results from a Prospective, Randomized, Controlled Pilot Study. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 562) Rathbun R, Farmer K, Stephens J, Lockhart S; Univ. of Oklahoma Hlth. Sci. Ctr., Oklahoma City, USA and 2Univ. of Oklahoma Schusterman Ctr., Tulsa, USA BACKGROUND: Adherence clinics have the potential to improve response to highly active antiretroviral therapy (HAART), but controlled trials are limited and do not account for regimen-related characteristics. A randomized, controlled pilot study was conducted to examine the effect of an adherence clinic on adherence and |
| 563 | Comparison of Directly Administered Antiretroviral Therapy in a Methadone Clinic and Self-Administered Therapy in HIV-infected Patients. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 563) Lucas G, Weidle P, Hader S, Moore R; Johns Hopkins Univ., Baltimore, MD, USA and 2CDC, Atlanta, GA, USA BACKGROUND: Methadone clinics provide settings where DAART may be feasible in HIV-infected drug users (DUs), but there are few data on the potential effectiveness of this approach. METHODS: Since April 2001, DUs who were receiving HIV care and methadone therapy at Johns Hopkins were enrolled in a prospective Directly A |
| 564 | A Virological Benefit from an Induction/Maintenance Strategy Compared with a Standard 3-drug Regimen in Antiretroviral Naïve Patients: the FORTE Trial Conf Retrovir Opportunistic Infect. 2004 Feb 8-11;11: (abstract No. 564 Williams I, Asboe D, Babiker A, Goodall R, Hooker M, and the FORTE Trial Steering Committee; Royal Free and Univ. Coll. Med. Sch., London UK BACKGROUND: Current 3-drug regimens fail to adequately suppress HIV RNA viral load in a significant proportion of patients starting ART so new strategies are needed to improve efficacy. FORTE is the first trial to report on an induction strategy with 4-drugs followed by a 3-drug regimen. Previous trial results with ind |
| 565 | Revisiting Maintenance Therapy: Evaluating HIV DNA and HIV RNA as Predictors of Virologic Success. Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11; 11:(abstract No. 565) Havlir DV, Bassett R, Li D, Pollard R, Richman D, Collier A, Tebas P, Hirsch M, Strain M, Ignacio CC, Wong JK; Univ. of California, San Francisco, USA BACKGROUND: Prior attempts to treat patients with induction-maintenance therapy were abandoned due to unacceptable rates of virologic failure. Subsequent studies show that some subjects sustain viral suppression for years with a boosted PI-only regimen. We reasoned that HIV DNA and more sensitive measures of HIV RNA (V |
| 566 |