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10th International Workshop on Adverse Drug Reactions
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Cite as: Antiviral Therapy 2008; 13(Supp. 4):x
where x is the page number
| Oral Presentations |
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| O-01 | DIFFERENTIAL ALTERATIONS OF GENE EXPRESSION IN VISCERAL VERSUS SUBCUTANEOUS ADIPOSE TISSUE FROM HIV-1-INFECTED, HAART-TREATED PATIENTS WITH LIPODYSTROPHY: A PILOT STUDY Antiviral Therapy 2008; 13(Supp. 4):A3 (abstract no. O-01 J Villarroya1, JM Gallego-Escuredo1, JC Domingo1, M Alegre2, MM Gutierrez2, MG Mateo2, F Villarroya1, P Domingo2 and M Giralt1 To our knowledge, this is the first study in which a gene expression analysis of VSA from HIV-1infected, HAART-treated patients with lipodystrophy is reported. Similar alterations in markers of mitochondrial function and inflammation in SCA and VSA from patients suggest that these processes are unlikely to be the main determinants of the differential behaviour of the two adipose depots in patients. No impairment in gene expression for marker genes of adipogenesis in VSA is consistent with the lack of atrophy of this depot and highlights the relevance of the adipogenic differentiation processes in the outcome of adipose tissue depots in response to viral and drug-induced insults. |
| O-02 | HIV PROTEASE INHIBITORS DIFFERENTLY AFFECT HUMAN SUBCUTANEOUS AND VISCERAL FAT: THEY INDUCE IL-6 PRODUCTION AND ALTER LIPID STORAGE CAPACITY IN SUBCUTANEOUS BUT NOT VISCERAL ADIPOSE TISSUE EXPLANTS Antiviral Therapy 2008; 13(Supp. 4):A3 (abstract no. O-02) C Vatier1,2, S Leroyer1,2, J Quette1,2, N Brunel3, J Capeau1,2 and B Antoine1,2 Our results show, that some PIs induce an inflammatory profile in human SCAT as indicated by increased IL-6 production. This resulted in decreased fatty acid re-esterification through the glyceroneogenesis pathway and increased fatty acid release. These alterations could help to understand the ART-related SCAT lipoatrophy and systemic hyperlipidaemy. Under similar conditions, VAT was resistant to the deleterious actions of PIs. These data are in accordance with the clinical discordant effect of ART in the two fat depots observed in HIV-related lipodystrophies. |
| O-03 | ACUTE EFFECTS OF RITONAVIR IN GLUT4 AND GLUT2 KNOCKOUT MICE Antiviral Therapy 2008; 13(Supp. 4):A4 (abstract no. O-03 J Koster1 and PW Hruz1,2 These data confirm that the acute effect of ritonavir on peripheral glucose disposal is mediated through direct inhibition of GLUT4 activity in vivo. In contrast, the effect of ritonavir on insulin secretion does not appear to be mediated by GLUT2 blockade. The ability of GLUT4 blockade to contribute to derangements in the other molecular pathways that influence insulin sensitivity remains to be determined. |
| O-04 | EFFECTS OF IGF-1/IGFBP-3 TREATMENT ON GLUCOSE METABOLISM AND FAT DISTRIBUTION IN HIV-INFECTED PATIENTS WITH ABDOMINAL OBESITY AND INSULIN RESISTANCE Antiviral Therapy 2008; 13(Supp. 4):A5 (abstract no. O-04) MN Rao1, K Mulligan1, J-M Schwarz1,2, VW Tai1, M Wen1, M Weinberg1, A Dyachenko2, T Lang1 and M Schambelan1 In this pilot study, treatment with IGF-1/ IGFBP-3 was associated with improvement in whole body glucose uptake and oral glucose tolerance. However, an increase in fasting EGP and blunted suppression during hyperinsulinemic euglycaemic clamp were also observed. Although lean body mass increased and total body fat decreased, visceral fat and lipid profiles were unchanged. |
| O-05 | ASSOCIATION OF C-REACTIVE PROTEIN AND HIV INFECTION WITH ACUTE MYOCARDIAL INFARCTION Antiviral Therapy 2008; 13(Supp. 4):A5 (abstract no. O-05 VA Triant1,2,3, JB Meigs4 and SK Grinspoon3 Increased CRP and HIV are independently associated with increased AMI risk, and HIV patients with increased CRP have a markedly increased risk of AMI compared with those with neither risk factor. Measurement of CRP may be useful in the cardiovascular risk assessment and prediction of AMI in HIV patients. |
| O-06 | RITONAVIR 100 MG TWICE DAILY, BUT NOT 100 MG ONCE DAILY, INCREASES ADIPOPHILIN EXPRESSION: POTENTIAL EFFECT OF RITONAVIR ON CARDIOVASCULAR DISEASE (CVD) Antiviral Therapy 2008; 13(Supp. 4):A6 (abstract no. O-06) M Boffito1, S Collot-Teixeira2, F De Lorenzo3, L Waters1, C Fletcher1, D Back4, S Mandalia1, A Pozniak1, J McGregor2,5 and B Gazzard1 In healthy volunteers, 100 mg twice daily ritonavir, but not 100 mg once daily ritonavir, led to an increase in adipophilin gene expression over 2 weeks; the increase was related to higher ritonavir exposure. Increased CD40L concentrations were measured for both ritonavir dosages. |
| O-07 | CAROTID INTIMA-MEDIA THICKNESS (cIMT) IMPROVES
OVER TIME IN HIV-INFECTED CHILDREN Antiviral Therapy 2008; 13(Supp. 4):A6 (abstract no. O-07 AC Ross1,2, N Storer1,2, MA O’Riordan1,2, V Dogra3, D El-Bejjani2, S Bhatt3 and GA McComsey1,2 At 48 weeks, cIMT improved in HIV-infected children. This might be due to the concurrent decrease in LDL-cholesterol and increase in CD4 counts. |
| O-08 | METABOLIC PROFILE OF TWO FIXED-DOSE NUCLEOSIDE ANALOGUE COMBINATIONS (TENOFOVIR/EMTRICITABINE VERSUS ABACAVIR/LAMIVUDINE): BICOMBO MET, A SUBSTUDY OF THE BICOMBO STUDY< Antiviral Therapy 2008; 13(Supp. 4):A7 (abstract no. O-08) M Saumoy1, J Ordoñez2, P Barragan1, E Martinez3, E Ribera4, R Bonet2, H Knobel5, E Negredo6, JM Gatell3 and D Podzamczer1 Quantitative lipid profile modifications were associated with the use of TDF/FTC and ABC/3TC. ABC/3TC was associated with a more atherogenic LDL cholesterol profile although estimated CV risk remained stable with both therapies. |
| O-09 | PATHOGENESIS OF LIPOATROPHY: ANALYSIS OF TISSUE AND PLASMA Antiviral Therapy 2008; 13(Supp. 4):A8 (abstract no. O-09 E Hammond, E McKinnon, S Mallal and D Nolan The study demonstrates that lipoatrophy shares a number of histopathological features with obesity, including adipose tissue inflammation and macrophage infiltration, although in this case adipocyte-specific mt toxicity appears to be a primary pathogenic mechanism. Those with most severe pathology appear to show the poorest recovery. |
| O-10 | SKELETAL MUSCLE MITOCHONDRIAL PROTEINS DISCORDANTLY REGULATED BY INSULIN IN HIV+ WITH INSULIN RESISTANCE: A MASS SPECTROMETRY-BASED MUSCLE PROTEOMICS STUDY Antiviral Therapy 2008; 13(Supp. 4):A8 (abstract no. O-10) KE Yarasheski, DN Reeds, S Smith, LY Munsell, J Malone, H Rohrs and RR Townsend These mt proteins represent potential biomarkers and sites of pathogenesis in HIV+ IR. The structure and function of the muscle intramitochondrial membrane and mt cristae might be altered in HIV+ IR. This could impair mt metabolite and ion flux, oxidative phosphorylation and mt ATP production during insulin stimulation. |
| O-11 | GREATER LIMB FAT INCREASE WITH INTERMITTENT (RELATIVE TO CONTINUOUS) THYMIDINE-SPARING ANTIRETROVIRAL THERAPY IN HIV-INFECTED PATIENTS WITH LIPOATROPHY Antiviral Therapy 2008; 13(Supp. 4):A9 (abstract no. O-11 E Martínez, A Milinkovic, F Garcia, E de Lazzari, M Larrousse, S Vidal, A León, M Lonca, M Laguno, M Martínez, M Calvo, JL Blanco, J Mallolas, JM Miró and JM Gatell In HIV-infected patients with lipoatrophy receiving thymidine-containing ART, intermittent thymidine-sparing ART leads to significantly greater increases in limb fat at 24 months than continuous thymidine-sparing ART. |
| O-12 | PROLONGED EXPOSURE TO HIV PROTEASE INHIBITORS (PIS) INDUCES PANCREATIC ISLET BETA-CELL DEATH AND DYSFUNCTION Antiviral Therapy 2008; 13(Supp. 4):A10 (abstract no. O-12) M Carper, S Zhang, WT Cade, K Yarasheski and S Ramanadham Taken together, these findings reveal for the first time that prolonged in vivo or in vitro exposure to some newer HIV PIs, despite promoting better serum lipid profiles, can cause beta-cell secretory dysfunction and beta-cell death by activating the mitochondrial, but not the ER stress, apoptotic pathway. In summary, our studies identify novel affects of HIV PI on pancreatic islet beta-cells and highlight the importance of considering beta-cell viability and function when assessing glycaemic control and diabetes in HIV-positive patients receiving PIs. |
| O-13 | INVOLVEMENT OF THE ADIPOCYTE RENIN-ANGIOTENSIN SYSTEM IN HIV PROTEASE INHIBITOR IN VITRO TOXICITY. BENEFICIAL EFFECT OF ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS Antiviral Therapy 2008; 13(Supp. 4):A10 (abstract no. O-13 F Boccara1,2,3, M Auclair1,2, A Cohen3, M Prott1,2, C Lefevre1,2, J Capeau1,2 and M Caron1,2 Our study demonstrates for the first time that, in vitro, the adipose RAS is upregulated and activated by PIs, probably via a PPARγ pathway. In vivo experiments are warranted to evaluate the potential beneficial effect of PPARγ-activating ARBs on the PI-induced lipodystrophic syndrome and insulin resistance. |
| O-14 | EFFECT OF INITIATION OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY ON INSULIN SENSITIVITY, AUTONOMIC NERVOUS SYSTEM FUNCTION AND BETA-ADRENERGIC MEDIATED LIPOLYSIS Antiviral Therapy 2008; 13(Supp. 4):A11 (abstract no. O-14) DN Reeds1, M Al-Lozi1, WT Cade1, BW Patterson1, WG Powderly2, KE Yarasheski1 and S Klein1 Short-term HAART causes insulin resistance, but does not affect basal lipolytic rates or the contribution of ß-adrenergic activity to lipolysis. In addition, HAART does not affect sympathetic or parasympathetic nervous system activity, but impairs SNS responsiveness. These data demonstrate that HAART likely causes insulin resistance in skeletal muscle, but not adipose tissue. The mechanisms responsible for these metabolic effects are not known, but it does not involve changes in autonomic nervous system activity. |
| O-15 | AUTONOMOUS NERVOUS SYSTEM ACTIVITY AND GLUCOSE METABOLISM IN HIV PATIENTS RECEIVING ANTIRETROVIRAL THERAPY Antiviral Therapy 2008; 13(Supp. 4):A11 (abstract no. O-15 M Wiese, M Kaspari, U Moebius, RE Schmidt and GMN Behrens To our knowledge these data provide the first evidence that low ANS activity might be associated with impaired glucose homeostasis in HIV patients receiving antiretroviral therapy. |
| O-16 | ß2-ADRENERGIC RECEPTOR POLYMORPHISMS ARE LINKED TO LIPOACCUMULATION WHILE A ß3-ADRENERGIC RECEPTOR POLYMORPHISM INFLUENCES LIPOATROPHY Antiviral Therapy 2008; 13(Supp. 4):A12 (abstract no. O-16) A Riva1, M Nasi2, BZ Poma1, P Cicconi3, S Martone1, AD Monforte3, A Cossarizza2 and M Galli1 Given the high prevalence of the polymorphism analysed and the relative low cost and feasibility of gene testing, it might be useful to determine the genetic predisposition of each single HIV-1-positive patient starting antiretroviral therapy. It could be possible to design individual regimens for each patient in order to avoid the rapid emergence of side effects and take adequate measures to delay their appearance. |
| O-17 | HIGH HIV VIRAL LOAD INHIBITS OSTEOBLAST FUNCTION AND SIGNALLING Antiviral Therapy 2008; 13(Supp. 4):A13 (abstract no. O-17 N Chew1,2,3, E Cotter1, P Doran1,3 and W Powderly1,2,3 These data demonstrate bioactivity of HIV in the setting of osteoblast cell culture. Serum obtained from HIV patients with high viral load effected significant changes in the bone phenotype, as evidenced by reduced capacity for calcium deposition. Intriguingly, this functional effect was mirrored by changes in the expression of the osteogenic transcription factor RUNX-2. These findings support the hypothesis that HIV itself, in addition to the well described effect of ART, can modulate bone phenotype and, at least in part, drive the osteopenia and osteoporosis, which is increasingly seen in HIV patients. |
| O-18 | EX VIVO MODULATION OF MESENCHYMAL STEM CELL FUNCTION IN HIV-1 INFECTION Antiviral Therapy 2008; 13(Supp. 4):A13 (abstract no. O-18) EJ Cotter1, N Chew1, WG Powderly2 and PP Doran1 Serum from HIV-1 patients both increased the degree of chemically induced adipogenesis from MSCs and drove the presentation of a pro-adipogenic phenotype in non-differentiating MSCs in a viral load-dependent manner. These findings underscore the hypothesis that perturbations in MSC cell differentiation are responsible, at least in part, for the observed toxicities seen in HIV patients in vivo. |
| O-19 | CONTINUOUS ANTIRETROVIRAL THERAPY DECREASES BONE MINERAL DENSITY: RESULTS FROM THE SMART STUDY Antiviral Therapy 2008; 13(Supp. 4):A14 (abstract no. O-19 B Grund1, G Peng1, R Isaksson1, K Ellis2, C Gibert3, J Shlay4, F Drummond5, E Martinez6, J Hoy7, P Reiss8, W El-Sadr9, A Thomas1, F Visnegarwala10, A Carr11 and the Body Composition Sub-study Investigators of the Strategies for Management of Anti-Retroviral Therapy (SMART) Study Continuous ART is associated with progressive decline in BMD and possibly more fractures relative to intermittent, CD4-guided ART. |
| O-20 | TOTAL BODY AND SPINE BONE MINERAL DENSITY ACROSS TANNER STAGES IN VERTICALLY HIV-INFECTED COMPARED WITH UNINFECTED CHILDREN AND YOUTH: PRELIMINARY RESULTS OF PACTG1045 Antiviral Therapy 2008; 13(Supp. 4):A15 (abstract no. O-20) DL Jacobson1, JC Lindsey1, GM Aldrovandi2, CM Gordon3, B Heckman4, A Zadzilka4, E Sheeran5, J Moye6, P Borum7, D Hardin8 and K Mulligan9 In this random sample of youth, HIV-pos males showed evidence of delayed bone density compared with HIV-neg males. The difference between the groups was most pronounced at the final stage of pubertal development. In contrast, there was no effect of HIV status on BMC or BMD among females. These data suggest that perinatally infected males might be at increased risk for bone disease during adulthood. |
| O-21 | EFFICACY OF A COMPUTERISED PHYSICIAN REMINDER SYSTEM TO CONTROL CARDIOVASCULAR RISK FACTORS IN HIV-INFECTED PATIENTS RECEIVING ANTIRETROVIRAL THERAPY (CART): A RANDOMISED CONTROLLED CLUSTER TRIAL NESTED INTO THE SWISS HIV COHORT STUDY (SHCS) Antiviral Therapy 2008; 13(Supp. 4):A15 (abstract no. O-21 HC Bucher1,2, M Rickenbach3, J Young1, TR Glass1, Y Vallet3, E Bernasconi4, M Cavassini5, C Fux6, V Schiffer7, P Vernazza8, R Weber9, M Battegay2, and the Swiss HIV Cohort Study Systemic, computerized, routine provision of CHD risk profiles in addition to guidelines did not significantly improve risk factors for CHD in patients on cART. |
| O-22 | COMPARISON OF DIRECTLY MEASURED AND ESTIMATED GLOMERULAR FILTRATION RATE IN PATIENTS WITH SUPPRESSIVE HAART INCLUDING ZIDOVUDINE, SWITCHING TO TENOFOVIR Antiviral Therapy 2008; 13(Supp. 4):A16 (abstract no. O-22) SME Vrouenraets1,2, E Fernandez Garcia2, FWNM Wit1,2, K Brinkman3, FJ Hoek1, RT Krediet1 and P Reiss1,2 on behalf of the PREPARE Study Group Mean mGFR decreased by almost 10% at 6 months after switch to tenofovir, therefore routine monitoring of renal function is warranted. In this small subset of patients with preserved renal function and suppressed HIV-infection, CG best reflected measured GFR and might be preferred over other estimates to monitor glomerular function in antiretroviral-treated patients. |
| O-23 | AIDS AND NON-AIDS DEFINING MALIGNANCIES IN HIV-INFECTED PATIENTS: THE 2006 ONCOVIH FRENCH STUDY Antiviral Therapy 2008; 13(Supp. 4):A17 (abstract no. O-23 E Lanoy1, JP Spano2, F Bonnet3, F Boué4, J Cadranel5, G Carcelain2, LJ Couderc6, P Frange7, PM Girard8, E Oksenhendler9, I Poizot-Martin10, C Semaille11, H Agut2, C Katlama1,2 and D Costagliola1,2 In 2006, almost two thirds of diagnosed malignancies in HIV-infected patients were non-AIDS defining. Malignancies were diagnosed in patients with a lower CD4+ T-cell count than the whole population of HIV-infected patients, even for non-AIDS malignancies. Patients with AIDS malignancies also more often had detectable plasma HIV RNA. This suggests that a better control of HIV and its associated immunodeficiency is required to prevent malignancies in HIV-infected patients. |
| O-24 | IMPAIRED MYOCARDIAL GLUCOSE METABOLISM IN MEN WITH HIV-ASSOCIATED METABOLIC SYNDROME Antiviral Therapy 2008; 13(Supp. 4):A17 (abstract no. O-24) WT Cade, DN Reeds, P Herrero, S Lassa-Claxton, RJ Gropler, LR Peterson and KE Yarasheski The myocardium in HIV+/MS+ appears insulin resistant compared with HIV+/MS-. FA extraction and metabolism were also impaired in HIV+/MS+. These findings imply greater myocardial lactate use in HIV+/MS+, but this requires further study. In HIV+/MS+, the heart’s ability to adapt to conditions requiring increased glucose or FA metabolism could be impaired. |
| O-25 | THE IMPACT OF RALTEGRAVIR AND LOPINAVIR/RITONAVIR ON PERIPHERAL GLUCOSE DISPOSAL IN HIV-NEGATIVE SUBJECTS Antiviral Therapy 2008; 13(Supp. 4):A18 (abstract no. O-25) P Randell, A Jackson, K Dennis and G Moyle In HIV-negative male subjects, 2 weeks of raltegravir was not associated with a significant impact on the M assessed during the euglycaemic clamp. In contrast, 2 weeks of lopinavir/ritonavir resulted in a significant reduction in the M, which is consistent with previously published findings. |
| Poster Presentations Adipocyte & Cell Biology |
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| P-01 | COMPARISON OF THE EFFECTS OF LOPINAVIR/RITONAVIR AND EFAVIRENZ ON GENE EXPRESSION AND DIFFERENTIATION OF HUMAN ADIPOCYTES Antiviral Therapy 2008; 13(Supp. 4):A23 (abstract no. P-01 J Diaz-Delfin1, JM Gallego-Escuredo1, M Milanski1, JC Domingo1, MM Gutierrez2, MG Mateo2, P Domingo2, M Giralt1 and F Villarroya1 Exposure of adipocytes to the lopinavir/ritonavir combination used in HAART impairs adipogenesis and increases inflammation-related gene expression, but to a lesser extent than equivalent amounts of efavirenz. Mitochondrial toxicity is not involved in these effects. Preferential induction of ER stress by lopinavir/ritonavir (4:1) does not appear to be associated with worsening the effects of this drugs combination on adipocyte biology with respect to efavirenz. |
| P-02 | CLINICAL CONCENTRATIONS OF EFAVIRENZ (EFV) REDUCE CELLULAR PROLIFERATION AND VIABILITY IN SEVERAL HUMAN CELL LINES Antiviral Therapy 2008; 13(Supp. 4):A23 (abstract no. P-02) N Apostolova1, A Blas-García2, D Ballesteros3, Y Gonzalez2, A Morán2, LJ Gómez-Sucerquia3 and JV Esplugues1 Clinical concentrations of EFV can be cytotoxic and lead to activation of apoptotic programmes in common cellular models. This suggests that the therapeutic range of EFV is rather narrow and also that prolonged administration of this drug could result in highly active antiretroviral therapy-related mitochondrial dysfunction. |
| P-03 | EFAVIRENZ INDUCES ALTERATIONS IN LIPID METABOLISM THROUGH AMPK ACTIVATION Antiviral Therapy 2008; 13(Supp. 4):A24 (abstract no. P-03 A Blas-García, D Ballesteros, D Monleón, JM Morales, M Rocha, VM Víctor, N Apostolova and JV Esplugues This metabolic stress promoted the activation of AMPK, triggering several of its signalling pathways, as EFV induced an increment in CD36 messenger RNA expression and in intracellular lipid content that could have been a result of the formation of lipid droplets. This intracellular lipid increase was not present in cells treated with compound C, which points to a key role for AMPK in these mechanisms. Given that EFV treatment is usually prolonged, these mechanisms might affect the general regulation of lipid metabolism and could cause the alterations that are characteristic of lipoathrophy. |
| P-04 | OPPOSITE EFFECTS OF NEVIRAPINE AND EFAVIRENZ ON DIFFERENTIATION AND GENE EXPRESSION OF HUMAN ADIPOCYTES IN CULTURE Antiviral Therapy 2008; 13(Supp. 4):A24 (abstract no. P-04) JM Gallego-Escuredo1, J Diaz-Delfin1, JC Domingo1, MM Gutierrez2, MG Mateo2, P Domingo2, M Giralt1 and F Villarroya1 Efavirenz impairs morphological adipogenic differentiation and adipogenic gene expression without causing mitochondrial toxicity. In contrast, nevirapine did not impair and even induced slight adipogenesis. Considering the evidence that alterations in the adipogenic processes take place in lipoatrophic adipose tissue from patients, inclusion of non-nucleoside reverse transcriptase inhibitors in antiretroviral regimes design should take into account the anti-adipogenic properties of efavirenz with respect to nevirapine. |
| P-05 | GENOME-WIDE TRANSCRIPTOMIC ANALYSIS REVEALS DISTINCT PATTERNS OF ALTERED GENE EXPRESSION IN SUBCUTANEOUS ADIPOSE TISSUE ASSOCIATED WITH HIV-1 INFECTION, ANTIRETROVIRAL TREATMENT AND LIPODYSTROPHY Antiviral Therapy 2008; 13(Supp. 4):A25 (abstract no. P-05 P Domingo1, JP Guallar2, JM Gallego-Escuredo2, J Díaz-Delfín2, JC Domingo2, M Alegre1, MM Gutierrez1, MG Mateo1, M Giralt2 and F Villarroya2 Alterations of gene expression in relation to immunity, inflammation and metabolism appear in adipose tissue from non-treated HIV-1-infected patients. Treated patients, in addition to disturbances in gene expression for those processes, show modifications in gene expression for metabolic pathways related to mitochondrial oxidation, macrophage activation and detoxification. Apoptosis-related gene expression is specifically altered in association with full-blown lipoatrophy. Present results highlight a role for HIV-1 infection in addition to antiretroviral treatment in eliciting adipose tissue alterations. Establishment of direct or indirect actions of HIV-1 on adipose tissue, identification of cellular actors other than macrophages as involved in the proinflammatory response of adipose tissue to HIV-1 infection and knowledge of the molecular basis for the specific alterations in energy metabolism appear as novel directions for research in HIV-1 lipodystrophy in the light of present findings. |
| P-06 | LEPTIN, A MARKER OF EVOLUTION TO LIPODYSTROPHY? RESULTS OF A 1-YEAR FOLLOW-UP IN HIV-INFECTED PATIENTS Antiviral Therapy 2008; 13(Supp. 4):A26 (abstract no. P-06) P Freitas1, D Carvalho1, C Gonçalves2, AC Santos3, MJ Matos1, S Xerinda4, R Marques4, F Correia1, R Serrão4, I Azevedo2, H Barros3, A Sarmento4 and JL Medina1 ADH and ghrelin, except leptin, showed a similar evolution on 1-year follow-up in HIV-infected patients with or without lipodystrophy. The decrease of leptin in patients without lipodystrophy seems to indicate a decrease in subcutaneous fat in these patients and could be a marker of progression to lipodystrophy. |
| P-07 | BMI AND LIPODYSTROPHY: A COMPLEX INTERPLAY ON ADIPOCYTE-DERIVED HORMONES ON HIV-INFECTED PATIENTS Antiviral Therapy 2008; 13(Supp. 4):A27 (abstract no. P-07 P Freitas1, D Carvalho1, C Gonçalves2, AJ Madureira3, AC Santos4, S Xerinda3, MJ Matos1, R Marques5, F Correia1, R Serrão5, I Azevedo2, I Ramos3, H Barros4, A Sarmento5 and JL Medina1 The lipodystrophy of HIV-infected patients is a complex model with an interplay of adiposity and fat redistribution on ADH. |
Insulin Resistance |
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| P-08 | INHIBITION OF THE INSULIN RECEPTOR KINASE BY ANTIRETROVIRAL PROTEASE INHIBITORS Antiviral Therapy 2008; 13(Supp. 4):A29 (abstract no. P-08) WIW Ismail and TS Pillay We conclude that the effects of HPIs to cause insulin resistance does not involve PTP1B or SOCS-1 protein, but may involve other regulatory proteins. |
| P-09 | THE IMPACT OF TENOFOVIR DISOPROXIL FUMARATE ON INSULIN SENSITIVITY, ADIPOCYTOKINES AND MARKERS OF ENDOTHELIAL FUNCTION Antiviral Therapy 2008; 13(Supp. 4):A29 (abstract no. P-09 P Randell1, A Jackson1, L Zhong2, K Yale2 and G Moyle1 Two weeks of TDF did not have any significant impact on insulin sensitivity, assessed by the M/I ratio during euglycaemic clamp, adipocytokines or markers of endothelial function. These results support the view that TDF has minimal metabolic impact and would be suitable as backbone treatment in metabolic studies in HIV-positive patients. |
| P-10 | ASSOCIATION OF SERUM VITAMIN D LEVELS AND TYPE 2 DIABETES IN HIV INFECTION IN THE MODENA COHORT Antiviral Therapy 2008; 13(Supp. 4):A30 (abstract no. P-10) Z Szep1, G Guaraldi2, S Shah1, G Orlando2, N Squillace2, V Rochira2, B Madeo2, C Diazzi2, E Baraldi2, GC Carani2, R Esposito2 and P Tebas1 Individuals with HIV and type 2 DM had significantly lower vitamin D levels in comparison with HIV infected individuals without type 2 DM. Patients with vitamin D deficiency were more likely to have type 2 DM in comparison with those with adequate vitamin D levels. Although causality cannot be inferred, vitamin D deficiency might be a modifiable risk factor for the development of type 2 DM among HIV-infected patients. |
| P-11 | THE IMPACT OF SWITCHING DOUBLE-BOOSTED PROTEASE INHIBITORS TO DARUNAVIR/RITONAVIR ON INSULIN SENSITIVITY Antiviral Therapy 2008; 13(Supp. 4):A30 (abstract no. P-11 P Randell, A Jackson, M Nelson and G Moyle In patients switching from a DBPI regimen to DRV/r, virological control was maintained after 4 weeks. Overall, there was no deleterious impact on insulin sensitivity with the switch and in patients with lower insulin sensitivity at baseline there was evidence of an improvement. There was no short-term effect on lipid homeostasis. |
| P-12 | LOW PHYSICAL FUNCTION IS ASSOCIATED WITH DIABETES MELLITUS AMONG HIV-INFECTED AND HIV-NEGATIVE MEN Antiviral Therapy 2008; 13(Supp. 4):A31 (abstract no. P-12) A Longenberger1, J Lim2, TJ Orchard1, M Brooks1, J Brach3, K Mertz1 and LA Kingsley1,4 This study suggests that low physical function (as a surrogate for physical activity) is associated with DM and IR in both HIV-infected and HIV-negative men. Future research using objective physical activity measures is warranted to further understand the contribution of low physical activity to DM and IR among HIV-infected populations. Ongoing HIV cohort studies should address the role of physical activity as an important contributor to impaired glucose metabolism. |
| P-13 | EFFECTS OF DIET AND EXERCISE AND/OR ROSIGLITAZONE ON BODY COMPOSITION AND GLUCOSE METABOLISM IN HIV-POSITIVE AND HIV-NEGATIVE SUBJECTS Antiviral Therapy 2008; 13(Supp. 4):A31 (abstract no. P-13 JB Albu, CM Kim, ES Engelson, TC Pitea and DP Kotler Weight loss and rosiglitazone are equally effective in improving glucose metabolism. HIV status did not affect treatment responses in obese, insulin resistant individuals in this study. |
Bone Metabolism & Toxicities |
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| P-14 | BONE MINERAL MASS LOSS RISK IN HIV-INFECTED PATIENTS ON HAART: A LONGITUDINAL STUDY Antiviral Therapy 2008; 13(Supp. 4):A33 (abstract no. P-14) G Madeddu1, A Spanu2, F Chessa2, GM Calia1, C Lovigu1, M Mannazzu1, A Falchi2, D Sanna2, F Cambosu1, G Ferrandu1, MS Mura1, G Madeddu2 This longitudinal study demonstrates that in HIV patients on HAART a decrease of BMD, even osteoporosis, can occur. Bone mass loss, when continuing treatment, persisted over time and further worsened in some of our cases, in particular when receiving PI. Thus, a correct bone metabolism follow-up is suggested in patients on HAART, even more when other risk factors are present, to early identify those cases to be submitted to appropriate preventive treatments to reduce fracture risk. |
| P-15 | ASSOCIATION BETWEEN PERIPHERAL LIPOATROPHY AND BONE DEMINERALIZATION IN TREATED HIV-POSITIVE MALES Antiviral Therapy 2008; 13(Supp. 4):A33 (abstract no. P-15 J Falutz and K Rosenthall Progressive loss of peripheral fat mass, unrelated to loss of lean mass, is associated with decreasing BMD in the hip region but not at the LS spine. This LA-associated bone demineralization may contribute to increasing hip-related morbidity in treated patients, especially as they age. Both total body and regional BMD assessment should be considered and efforts to prevent and treat peripheral LA instituted where possible. |
| P-16 | ASYMPTOMATIC OSTEONECROSIS OF THE HIP IN HIV-INFECTED PATIENTS Antiviral Therapy 2008; 13(Supp. 4):A34 (abstract no. P-16) JL Lamas1, A Ocampo1, C Miralles1, R Longueira1, MT Pérez1, A Casal2, J Corroto2, M Arias2, B Sopeña1, A Rivera1 and C Martínez Vázquez1 The prevalence of asymptomatic OTNH in HIV-infected patients was 4.1%. The most important risk factors for OTNH were corticosteroid treatment, a lower CD4 lymphocyte nadir and AIDS-defining disease. In this group of patients, ARV treatment was not associated with the presence of osteonecrosis. |
Body Composition |
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| P-17 | LONG-TERM CHANGES IN BODY FAT AND BONE MASS DENSITY AFTER SWITCHING FROM NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS TO FIXED-DOSE TENOFOVIR/EMTRICITABINE OR ABACAVIR/LAMIVUDINE Antiviral Therapy 2008; 13(Supp. 4):A35 (abstract no. P-17 A Curran1, P Barragan2, M Loncà3, M Crespo1, E Martinez3, M Piron1, E Ferrer2, D Podzamczer2, JM Gatell3 and E Ribera1 After 96 weeks of follow-up, switching from NRTI to either TE or AL similarly increased limb fat and BMD. |
| P-18 | LIMB FAT CHANGES 48 WEEKS AFTER SWITCHING FROM AZT/3TC TO FTC/TDF VERSUS CONTINUING ON AZT/3TC. PRIMARY ENDPOINT ANALYSIS OF THE RECOMB TRIAL Antiviral Therapy 2008; 13(Supp. 4):A35 (abstract no. P-18) E Martínez1, E Ribera2, B Clotet3, V Estrada4, J Sanz5, J Berenguer6, R Rubio7, F Pulido7, M Larrouse1, A Curran2, E Negredo3, S Arterburn8, P Ferrer9 and ML Alvarez9 Through 48 weeks, switching from AZT/3TC to FTC/TDF was well tolerated, efficacy was maintained and significant improvements in overall limb fat content were observed. Switching to FTC/TDF significantly increased limb fat at week 48 compared with AZT/3TC for patients with BL limb fat content <7.2 kg, those with prolonged exposure to AZT and patients with BL body mass index ≤25 kg/m2. |
| P-19 | EFFECTS OF TESAMORELIN (TH9507), A GROWTH HORMONE-RELEASING FACTOR (GRF) ANALOGUE, ON VISCERAL ADIPOSE TISSUE (VAT) IN HIV-INFECTED PATIENTS WITH EXCESS ABDOMINAL FAT: IMPACT OF ANTIRETROVIRAL THERAPY REGIMEN Antiviral Therapy 2008; 13(Supp. 4):A36 (abstract no. P-19 J Falutz1, J-C Mamputu2, C Marsolais2, D Potvin2, M Zoltowska2, D Aeschliman2, D Kotler3 and S Grinspoon4 The results of this study indicate that daily administration of 2 mg tesamorelin is useful for reducing VAT in HIV-infected patients with excess abdominal fat on ART, regardless of type of ART regimen. |
| P-20 | A PATHOGENESIS PROPOSAL OF LIPOATROPHY REVERSIBILITY AFTER SWITCHING FROM THYMIDINE ANALOGUES TO TENOFOVIR Antiviral Therapy 2008; 13(Supp. 4):A37 (abstract no. P-20) A Milinkovic, AI Garcia, I Perez, S Vidal, C Ayuso, M Laguno, A Leon, JL Blanco, M Martinez, M Lonca, M Larrousse, E Martinez, JM Gatell, X Tomas and J Mallolas Switching from thymidine analogues to TDF leads to significant reversal of peripheral lipoatrophy and lipid values improvement, whereas lean mass decreased when measured by DEXA. Correlations were observed between peripheral fat gain, loss of peripheral lean mass and decrease of IMCL and increase of EMCL lipid content. |
| P-21 | THE RELATION BETWEEN DURATION OF ZIDOVUDINE (ZDV) USE AND LIMB FAT CONTENT IS DEPENDENT ON WHETHER USED IN COMBINATION WITH A BOOSTED PROTEASE INHIBITOR (PI) OR WITH A NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR (NNRTI) Antiviral Therapy 2008; 13(Supp. 4):A37 (abstract no. P-21 SME Vrouenraets1,2, E Fernandez Garcia2, M Huber3, K Brinkman4, G Moyle5, P Domingo6, PE Tarr7, D Podzamczer8, M Ristola9, JM Gatell10, JM Livrozet11, FWNM Wit1,2, H Furrer12 and P Reiss1,2 for the PREPARE Study Group Longer duration of zidovudine exposure increases the likelihood of subcutaneous fat loss and possibly visceral adipose tissue gain. This association is most pronounced when combined with a PI and less with either efavirenz or nevirapine. |
| P-22 | URINE F2-ISOPROSTANE IS POSITIVELY CORRELATED WITH TRUNK AND TOTAL BODY FAT IN HIV-INFECTED, PROTEASE INHIBITOR-TREATED PERSONS WITH LOW TRADITIONAL CARDIOVASCULAR RISK PROFILE Antiviral Therapy 2008; 13(Supp. 4):A38 (abstract no. P-22) M Boger1, G Milne2, H Erdem1, V Mitchell1, D Haas1 and T Hulgan1 In this pilot study of non-smoking, nondiabetic ART-treated patients, urine IsoP-M, a marker of systemic oxidant stress associated with CVD risk, correlated with DEXA-derived measures of trunk and total body fat, and these correlations were strongest in persons receiving PI-based ART. Future studies should assess eicosanoids and other measures of lipodystrophy, other metabolic complications and CVD outcomes. |
| P-23 | OBJECTIVE AMOUNT OF LIMB FAT IN HIV-INFECTED SUBJECTS WITH SUBJECTIVE DIAGNOSIS OF LIPOATROPHY Antiviral Therapy 2008; 13(Supp. 4):A39 (abstract no. P-23 E Martínez1, M Larrousse1, D Podzamczer2 and JM Gatell1 The diagnosis of lipoatrophy was highly coincidental with the amount of limb fat irrespectively of the investigators. HIV-infected males with clinically evident lipoatrophy had more than 50% of their limb fat lost compared with non-HIV-infected healthy males. |
| P-24 | RESTING ENERGY EXPENDITURE AND SUBSTRATE UTILIZATION IN AIDS PATIENTS WITH LIPODYSTROPHY SYNDROME Antiviral Therapy 2008; 13(Supp. 4):A39 (abstract no. P-24) HS Vassimon1, AA Jordão Jr1, AA Machado1, FJA Paula1 and JP Monteiro2 Lipodystrophy syndrome could, independently, be a determinant of high energy expenditure in HIV patients. Also HIV patients with or without LS have a higher carboydrate utilization. |
| P-25 | BONE MARROW MAGNETIC RESONANCE IMAGING CHANGES IN HIV-INFECTED SUBJECTS WITH LIPODYSTROPHY Antiviral Therapy 2008; 13(Supp. 4):A40 (abstract no. P-25 AI García1, A Milinkovic2, X Tomás1, J Rios3, S Vidal4, J Pomés1, M Del Amo1 and J Mallolas2 HIV-infected patients with lipodystrophy syndrome may present no malignant bone marrow MR changes in the peripheral skeletal, especially legs, in correlation with the peripheral lipoatrophy. These findings may be related to a decrease in the fat bone marrow component, which probably needs more time to recover after switching from TA to TDF. It is important to be aware of these findings to avoid diagnostic mistakes. |
| P-26 | METABOLIC AND ANTHROPOMETRIC CHARACTERISTICS OF TVD, CBV OR KVX ASSOCIATED WITH NEVIRAPINE. RESULTS FROM THE ‘NEVIRAPINE COMPANION’ PROSPECTIVE COHORT Antiviral Therapy 2008; 13(Supp. 4):A41 (abstract no. P-26) G Guaraldi1, S Zona1, C Sconiamilio2, N Squillace1, G Orlando1, C Stentarelli1 and R Esposito1 The change of metabolic and anthropometric variables were not predicted by TVD, CBV or KVX arms associated with nevirapine. We confirmed traditional risk factors for anthropometric and metabolic variables: male gender for both lipoatrophy and central fat accumulation and BMI for lipids and glucose abnormalities. KVX arm, in which was documented a poor metabolic profile at cross-section evaluation, does not display a disadvantage in the evolution of metabolic and anthropometric variables. |
| P-27 | DIFFERENT METABOLIC AND ANTHROPOMETRIC CHARACTERISTICS OF TVD, CBV OR KVX ASSOCIATED WITH NEVIRAPINE. RESULTS FROM THE ‘NEVIRAPINE COMPANION’ CROSS-SECTIONAL COHORT Antiviral Therapy 2008; 13(Supp. 4):A41 (abstract no. P-27 G Guaraldi1, F Adorni2, C Sconiamilio3, S Zona1, N Squillace1, G Orlando1, C Stentarelli1 and R Esposito1 KVX arm displayed a grater pro-atherogenic risk profile not withstanding lower body mass index in respect to CBV and TVD. This non-randomized cohort cannot discriminate if patients with a higher underlying risk of cardiovascular disease might be initially placed on KVX or if KVX associated with NVP per se had a poorer metabolic profile compared with the TVD and CBV arms. Careful assessment of metabolic parameters should be evaluated in people undergoing the association KVX+NEV even beyond initial 6 months of therapy and appropriated lipid-lowering therapy started if needed. |
Lipid Metabolism |
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| P-28 | FRIEDEWALD’S EQUATION UNDERESTIMATES LDL ELEVATIONS FOR PATIENTS WITH HIGH TRIGLYCERIDE LEVELS IN THE ARTEMIS AND TITAN TRIALS Antiviral Therapy 2008; 13(Supp. 4):A43 (abstract no. P-28) M Nelson1, R DeMasi2, C Moecklinghoff3 and A Hill4,5 The Friedewald equation underestimated the incidence of calculated LDL elevations in the LPV arms of the ARTEMIS and TITAN trials. Setting a TG value of 4.52 mmol/l (400 mg/dl) for samples with high TG levels detects more elevations of calculated LDL. |
| P-29 | METABOLIC CHANGES AND CARDIOVASCULAR RISK AFTER SWITCHING FROM LOPINAVIR/R TO ATAZANAVIR/R: METATAZIP, A SUBSTUDY OF THE ATAZIP STUDY Antiviral Therapy 2008; 13(Supp. 4):A43 (abstract no. P-29 E Ferrer1, M Saumoy1, J Ordoñez2, A Milinkovic3, P Domingo2, E Ribera4, E Negredo5, J Curto1, JM Gatell3 and D Podzamczer1 Switching from LPV/r to ATV/r was associated with a favourable lipid profile and a decrease in estimated CV risk. |
| P-30 | EARLY IMPROVEMENT OF TRIGLYCERIDES AND LDL-CHOLESTEROL LEVELS IN DYSLIPIDAEMIC HIV-INFECTED PATIENTS AFTER SWITCHING NRTI BACKBONE TO TENOFOVIR PLUS EMTRICITABINE: THE TOTEM RANDOMIZED TRIAL Antiviral Therapy 2008; 13(Supp. 4):A44 (abstract no. P-30) M-A Valantin1, P De Truchis2, R Bittar1, D Bollens3, L Slama4, B Lebouché5, P Pétour6, C Aubron-Olivier6, D Costagliola7 and C Katlama1 on behalf of the TOTEM study group In dyslipidaemic HIV-1-infected controlled patients, switching the NRTI backbone to tenofovir/emtricitabine significantly improved TG and LDL-C levels over 12 weeks, with a significant improvement noted as early as 4 weeks and more patients normalizing LDL-C by week 12. |
| P-31 | HIV INFECTION SIGNIFICANTLY REDUCES LIPOPROTEIN LIPASE WHICH REMAINS LOW AFTER 6 MONTHS OF ANTIRETROVIRAL THERAPY Antiviral Therapy 2008; 13(Supp. 4):A45 (abstract no. P-31 M Boothby1, AM Umpleby2, F Shojaee-Moradie2, JW Tomlinson3, LL Gathercole3, K McGee4, S Das5 and M Shahmanesh1 Post-heparin LPL activity is reduced in HIV and does not return to control levels after 6 months of ARV therapy. Regimens containing AZT are associated with a greater increase in LPL, LPL gene expression and plasma adiponectin than TDF. |
| P-32 | SAQUINAVIR VERSUS ATAZANAVIR ONCE DAILY, EACH BOOSTED WITH 100 MG RITONAVIR AND COMBINED WITH TENOFOVIR/EMTRICITABINE, RESULT IN COMPARABLE LIPID CHANGES AFTER 24 WEEKS IN TREATMENT-NAÏVE HIV-INFECTED PATIENTS Antiviral Therapy 2008; 13(Supp. 4):A46 (abstract no. P-32) SME Vrouenraets1,2, E Fernandez Garcia2, A Jackson3, F Raffi4, DT Jayaweera5, C Katlama6, M Fisher7, L Slama8, D Hardy9, S Mauss10, E DeJesus11, A van Eeden12, D Prelutsky13, FWNM Wit1,2, G Moyle3 and P Reiss1,2 for the BASIC Study Group When combined with tenofovir/emtricitabine, SQV/r 2,000/100 mg once daily and ATV/r 300/100 mg once daily have similar modest effects on lipids over 24W, with comparable virological and immunologic efficacy in treatment-naïve patients. |
| P-33 | A RANDOMIZED COMPARATIVE STUDY OF THE IMPACT OF TENOFOVIR, LAMIVUDINE PLUS LOPINAVIR/R OR FOSAMPRENAVIR/R TWICE DAILY ON LIPOPROTEIN SUBFRACTIONS IN PERSONS INITIATING ANTIRETROVIRAL THERAPY Antiviral Therapy 2008; 13(Supp. 4):A46 (abstract no. P-33 P Randell, A Jackson, J Taylor and G Moyle Commencing tenofovir, lamivudine plus either lopinavir/r twice daily or fosamprenavir/r twice daily in HIV-1 patients is associated with a shift towards an ‘atherogenic lipoprotein pattern’ typified by an increase in small LDL particles, a decrease in large LDL particles and accompanied by an increase in triglycerides and a decrease in HDL cholesterol. This was not associated with changes in insulin sensitivity. |
| P-34 | EFFECT OF SPECIFIC ANTIRETROVIRAL THERAPY (ART) DRUGS ON LIPID CHANGES AMONGST HIV-INFECTED CHILDREN IN TWO CLINICS IN LONDON Antiviral Therapy 2008; 13(Supp. 4):A47 (abstract no. P-34) C Smith1, M Rhoads2, J Lanigan3, H Lyall2, K Doerholt4, A Judd4 and D Gibb4 TC levels were generally higher amongst those exposed to any of the four drugs, especially for <1 year’s exposure, before declining again in later years. This is perhaps because of treatment switches amongst those with the highest levels. Additionally, much of this TC increase appeared driven by beneficial HDL increases, particularly for NVP and EFV. Measuring surrogate CVD markers such as lipids over time may be a useful tool in assessing the likely impact of life-long ART on CVD risk in this population. |
| P-35 | LIPID CHANGES IN PATIENTS RECEIVING NEVIRAPINE (NVP) IN COMBINATION WITH TENOFOVIR/EMTRICITABINE: RESULTS FROM THE CCIAT TRIAL Antiviral Therapy 2008; 13(Supp. 4):A48 (abstract no. P-35 C Davis1,2, R Talwani1,2, B Gilliam1,2, A Amoroso1,2, C Boyce1, S Storfer3, C Conner3, R Redfield1,2 The combination of NVP plus TDF/FTC resulted in favourable effects on serum lipids, with a significant increase in HDL-c, a significant decrease in TGs and non-significant change in LDL-c and TC. This regimen appears to improve the cardiovascular risk profile of patients taking ARV therapy. |
| P-36 | MICRONUTRIENT SUPPLEMENTATION INCREASES APOLIPOPROTEIN A1 LEVELS IN PERSONS LIVING WITH HIV Antiviral Therapy 2008; 13(Supp. 4):A49 (abstract no. P-36) E Morgan and W Wobeser As demonstrated in previous studies, HIV infection is associated with decreased serum HDL-C levels, as well as lower levels of ApoA1. Our results suggest that supplementation with specific micronutrients may increase levels of ApoA1 in persons living with HIV. This increase was comparable to levels associated with decreased cardiac risk in population studies. While further research is needed to determine the clinical significance of these changes, the indirect evidence for an antiatherogenic, immunomodulatory and antiviral effects of HDL-C mediated by ApoA1 is intriguing and understudied. Micronutrient supplementation may represent a relatively safe and non-resistanceinducing adjunct to both increase the efficacy and help alleviate the adverse effects of HIV treatment. |
| P-37 | SWITCHING HIV-INFECTED, SUPPRESSED PATIENTS FROM ABC/3TC TO FTC/TDF IMPROVES LIPIDS – THE SETTLE STUDY Antiviral Therapy 2008; 13(Supp. 4):A49 (abstract no. P-37 JC Gathe, Jr Switching to FTC/TDF demonstrated significant lipid reductions evident through week 12 and the proportion of patients meeting NCEP guidelines remained improved by week 48. This suggests switching to FTC/TDF therapy may play a role in minimizing metabolic side effects related to HAART. The ongoing SWIFT study is examining patients switching from EPZ to TVD versus continued EPZ. Results from SWIFT should further elucidate potential benefits. |
Cardiovascular Disease |
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| P-38 | SOME PROTEASE INHIBITORS INDUCE HUMAN ENDOTHELIAL CELL DYSFUNCTION AND PRELAMIN A ACCUMULATION Antiviral Therapy 2008; 13(Supp. 4):A51 (abstract no. P-38) C Lefèvre1,2, F Boccara1,2,3, M Auclair1,2, J Capeau1,2 and M Caron1,2 Our results show that a chronic incubation of human endothelial cells with ritonavir or the combination atazanavir/ritonavir could alter endothelial cell function by decreasing NO bioavailability and increasing ROS production. These PIs also trigger prelamin accumulation, a phenotype associated with premature senescence. These results indicate that some PIs could have a direct effect on the endothelial cell system, ultimately leading to endothelial dysfunction and premature senescence. These alterations are probably involved in increased cardiovascular risk. |
| P-39 | PROTEASE INHIBITORS LOPINAVIR AND INDINAVIR DO NOT INDUCE LEUKOCYTE–ENDOTHELIAL CELL INTERACTIONS IN THE MICROVASCULATURE Antiviral Therapy 2008; 13(Supp. 4):A51 (abstract no. P-39 MM Andrade1,2, C De Pablo-Bernal1, JV Esplugues1,3 and A Álvarez1,3 These studies indicate that acute exposure to lopinavir and indinavir does not induce leukocyte recruitment, and suggest that lopinavir and indinavir are not responsible of precipitating the cardiovascular diseases observed in HIV-infected patients treated with PIs as part of combined antiretroviral therapy. |
| P-40 | LONGITUDINAL EVALUATION OF CARDIOVASCULAR DISEASE-ASSOCIATED BIOMARKERS IN RELATION TO ABACAVIR THERAPY Antiviral Therapy 2008; 13(Supp. 4):A52 (abstract no. P-40) E Hammond, E McKinnon, S Mallal and D Nolan No significant change in biomarker profile known to be related to cardiovascular risk was detected in association with abacavir use. In fact, all significant changes from baseline appeared beneficial, possibly attributable to either anti-HIV effects or cessation of thymidines. |
| P-41 | FACTORS ASSOCIATED WITH HYPERHOMOCYSTEINAEMIA Antiviral Therapy 2008; 13(Supp. 4):A52 (abstract no. P-41 B Roca, J Ferrero, M Bennasar and MC del Monte Hyperhomocysteinaemia was common among the HIV-infected patients of our cohort. We found an association of higher levels of homocysteine with male gender and lower HDL-cholesterol levels. |
| P-42 | MIF (MACROPHAGE MIGRATION INHIBITORY FACTOR): A POTENTIAL BIOMARKER FOR CARDIOVASCULAR DISEASE IN PERSONS WITH HIV? Antiviral Therapy 2008; 13(Supp. 4):A53 (abstract no. P-42) IJ Woolley1,2, S Ayoub1, SM Crowe1,3, CL Cherry2,3, K Visvanathan1,3 and E Morand1 MIF is a noted cardiovascular biomarker. It has been shown to correspond with probable inflammation due to HIV-related viraemia and would be a suitable biomarker for case-control studies in cardiovascular disease in HIV. |
| P-43 | EFFECT OF PIOGLITAZONE ON MYOCARDIAL GLUCOSE AND PALMITATE METABOLISM IN HIV-ASSOCIATED METABOLIC SYNDROME: A PRELIMINARY REPORT Antiviral Therapy 2008; 13(Supp. 4):A53 (abstract no. P-43 WT Cade, DN Reeds, P Herrero, S Lassa-Claxton, RJ Gropler, LR Peterson and KE Yarasheski Preliminary findings indicate that PIO improves whole-body insulin sensitivity and has a tendency to increase myocardial FA utilization and oxidation, without increasing myocardial glucose utilization rate. This may reflect a predominant PPARα-agonist action of PIO in the heart. It might be metabolically beneficial because baseline myocardial FA utilization rates were lower in HIV+MS than healthy controls. Cardiac contractile function was unchanged after 16 weeks of PIO. The long-term effects and mechanism of action of PIO on myocardial function and substrate utilization requires further study. |
| P-44 | CAN CHANGES IN PROINFLAMMATORY CYTOKINES AND ENDOTHELIAL ACTIVATION MARKERS AFTER HAART PREDICT SUBSEQUENT CORONARY ARTERY DISEASE (CAD)? Antiviral Therapy 2008; 13(Supp. 4):A54 (abstract no. P-44) AC Ross1,2, TT Brown3, MA O’Riordan1, Y Tang3 and GA McComsey1,2 HIV-positive individuals with CAD had similar changes in proinflammatory cytokines and endothelial activation markers after 2 years of HAART when compared with HIV-positive individuals without CAD. Larger studies investigating earlier time points after HAART initiation are needed to confirm these findings. |
| P-45 | SUBCLINICAL CORONARY ARTERY ATHEROSCLEROSIS AND ENDOTHELIAL DYSFUNCTION ARE NOT PREDICTORS OF ERECTILE DYSFUNCTION IN HIV-INFECTED MALES Antiviral Therapy 2008; 13(Supp. 4):A55 (abstract no. P-45 S Zona1, K Luzi1, R Murri2, A Granata1, G Orlando1, N Squillace1, G Ligabue3, V Rochira4, R Rossi4 and G Guaraldi1 In HIV-infected people, aesthetic satisfaction of the face and age, but not CAC and FMD, were predictors of ED. |
| P-46 | CAROTID VESSELS LESIONS IN EXPERIENCED HIV-1 INFECTED SUBJECTS AFFECTED OR NOT BY HYPERTENSION AND/OR DIABETES MELLITUS Antiviral Therapy 2008; 13(Supp. 4):A55 (abstract no. P-46) G Semeraro1, M Guffanti1, MC Giusti2, L Galli1, S Salpietro1, A Lazzarin1 and A Castagna1 In this study 52% of individuals not affected by diabetes and/or hypertension showed an increased IMT and 15% had fibrous or dishomogeneous plaques. These findings strengthen usefulness of a screening with ultrasonographic examination of epiaortic vessels in HIV-1-infected individuals, even if free of co-morbidity, especially if they are older or treated with lipid-lowering drugs. In presence of fibrous wall degeneration (IMT>1), a well known indicator of increased cardiovascular risk, periodic follow-up is warranted to evaluate the course of the carotid vessels lesions. |
| P-47 | AORTIC STIFFNESS DETERMINANTS IN HIV-INFECTED PATIENTS Antiviral Therapy 2008; 13(Supp. 4):A57 (abstract no. P-47 F Boccara1, E Catez1, S Lang1, M Ferron1, S Ederhy1, C Meuleman1, C Duvivier2, M Kirstetter3, PM Girard3, G Pialoux3, C Katlama3 and A Cohen1 Our study showed that in this cohort of HIV-infected patients, with a long duration of HIV infection and exposure to the last generation of PIs, aortic stiffness was related to traditional cardiovascular risk factors. |
| P-48 | HEART RATE AND BLOOD PRESSURE BEFORE AND AFTER KNOWING BLOOD ANALYSES RESULTS Antiviral Therapy 2008; 13(Supp. 4):A57 (abstract no. P-48) B Roca, MC del Monte, ME Celades, CM Evaristo, JJ Fancio and G Cebrian The anxiety that HIV-infected patients experience when they are about to be informed of their blood analyses results frequently provokes an increase in systolic blood pressure. |
| P-49 | BLOOD PRESSURE (BP): INFLUENCE OF BOOSTED ATAZANAVIR AND LOPINAVIR Antiviral Therapy 2008; 13(Supp. 4):A58 (abstract no. P-49 E Deig1, P García1, I Vidal1 and E Pedrol1,2 The findings in our pilot study were similar to other studies, showing a progressive increase in BP, especially SBP. Patients treated with ATV presented a lower non-significant increase of SBD and a non-significant decrease of DBP compared with those treated with LPV. |
| P-50 | METABOLIC SYNDROME IN HIV-POSITIVE NAÏVE PATIENTS: THE HERMES STUDY Antiviral Therapy 2008; 13(Supp. 4):A58 (abstract no. P-50) P Bonfanti1, E Ricci1, Orofino2, C Martinelli3, M Franzetti4, G De Socio5, P Marconi6, G Madeddu7, F Vichi8, P Vitiello1, L Valsecchi1, G Penco9 and T Quirino10 The high prevalence of the lipid components of MS in our cohort provides support to earlier suggestions that these modifications can be induced by the HIV infection per se. The increased risk of MS observed in patients with AIDS or with a more aggressive infection confirms this data. |
| P-51 | VIROLOGICAL FAILURE AND METABOLIC SYNDROME IN PATIENTS WITH HIV INFECTION Antiviral Therapy 2008; 13(Supp. 4):A59 (abstract no. P-51 N Squillace, S Zona, G Orlando, C Stentarelli, B Beghetto, G Nardini and G Guaraldi Our study highlights that HIV-infected patients experiencing virological failure are more at risk to develop MS. It is necessary to obtain virological suppression to prevent AIDS-related opportunistic infections, but also cardiovascular events and diabetes related to MS. |
| P-52 | STATISTICAL AGREEMENT BETWEEN METABOLIC SYNDROME ATP-III, IDF, EGIR AND ACE CLASSIFICATION IN HIV-INFECTED PATIENTS AND ASSOCIATION WITH BODY FAT REDISTRIBUTION Antiviral Therapy 2008; 13(Supp. 4):A59 (abstract no. P-52) N Squillace, S Zona, G Guaraldi, C Stentarelli, G Orlando, R D’amico, I Mazeu, and R Esposito Concordance between MS classification is less than ideal. The impact of body mass index and visceral adipose tissue/total adipose tissue is high for any MS definition. Visceral adipose tissue/total adipose tissue appears to be more predictive of MS according to ATP-III definition, but the higher prevalence of lipoatrophy in our sample (45%) could have been interfered with this result. Lipodystrophy phenotypes are associated to MS diagnosis especially using EGIR and ACE definitions. |
| P-53 | A COMPARISON OF CARDIAC FUNCTION BETWEEN HIV-INFECTED AND HIV-SERONEGATIVE PEOPLE WITH AND WITHOUT METABOLIC SYNDROME Antiviral Therapy 2008; 13(Supp. 4):A61 (abstract no. P-53 WT Cade, L de las Fuentes, K Mondy, DN Reeds, V Davila-Roman, A Waggoner, S Lassa-Claxton, P Herrero, KE Yarasheski and LR Peterson Impaired diastolic function was noted in HIV+ and HIV-with MS. Impaired systolic function was noted in HIV+MS and in HIV as a group. It appears that metabolic complications are associated with diastolic dysfunction, but HIV infection and/or HAART may strengthen this association. HIV infection is associated with subclinical systolic dysfunction, irrespective of the presence of metabolic complications. |
| P-54 | LIPOATROPHY AND LIPOHYPERTROPHY ARE ASSOCIATED WITH INCREASED PREDICTED 10-YEAR CARDIOVASCULAR RISK Antiviral Therapy 2008; 13(Supp. 4):A61 (abstract no. P-54) HM Crane1, C Grunfeld2, RD Harrington1 and MM Kitahata1 The Framingham 10-year CVDR provides the opportunity to evaluate overall CVDR rather than focusing only on individual risk factors, which may differ by body morphology. We found that lipoatrophy and lipohypertrophy are independently associated with higher predicted 10-year CVDR. Patients with both lipoatrophy and lipohypertrophy had the highest predicted risk. Further studies including longitudinal follow-up, better understanding of mechanisms and determining the effect on CVDR of risk factor modification are needed. In the interim, providers should consider perfoming CVDR profiling on HIV-infected patients with lipoatrophy or lipohypertrophy. |
| P-55 | CARDIOVASCULAR RISK ESTIMATION IN SPANISH HIV-INFECTED PATIENTS: A MULTICENTRE COHORT STUDY Antiviral Therapy 2008; 13(Supp. 4):A62 (abstract no. P-55 E Ferrer1, C Minguez2, A Mariño3, P Geijo4 F Brun5, J Sanz6, M Velasco7, C Cortés8, A Castro9, A Ortí10, Ll Force11, P Barrufet11, C Villalonga12 and D Podzamczer1 for the RICO study Traditional cardiovascular risk factors are associated with increased eCVR in our HIV population, and seem to have a stronger role than highly active antiretroviral therapy and HIV infection. Lower eCVR in patients with detectable viral loads is probably related to younger age, lower waist circumference and systolic blood pressure, and a better lipid profile. Patients with higher eCVR may benefit from lipid-friendly antiretroviral therapy, but interventions on life habits are crucial. |
Mitochondrial Disorders |
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| P-56 | IN VITRO ALTERATIONS IN HEPATOCYTE MITOCHONDRIAL RNA EXPRESSION AND DNA CONTENT FOLLOWING LONG-TERM EXPOSURE TO REVERSE TRANSCRIPTASE INHIBITOR COMBINATIONS Antiviral Therapy 2008; 13(Supp. 4):A65 (abstract no. P-56) TE Barnes1 and PWG Mallon1,2 These experiments demonstrate expected decreases in mtDNA with exposure to physiological concentrations of d4T/3TC with corresponding increases in mitochondrial and nuclear gene expression, which could be compensatory in nature. The contrasting decrease in MTCO1 expression seen with exposure to AZT/3TC and ABC/3TC, and the lack of correlation between MTCO1 expression and mtDNA content suggest an alternative route for these drug toxicities that is not mediated through mtDNA. To our knowledge, decreases in mtRNA expression with ABC/3TC have not been previously described. The strong correlations between mitochondrial and PPARγ gene expression have been previously observed in vivo and warrant further investigation. |
| P-57 | URIDINE SUPPLEMENTATION WITH MITOCNOL ATTENUATES MITOCHONDRIAL CARDIOMYOPATHY INDUCED BY ZIDOVUDINE AND ZALCITABINE Antiviral Therapy 2008; 13(Supp. 4):A65 (abstract no. P-57 K Balcarek1, D Lebrecht1, C Deveaud2, B Beauvoit2, J Bonnet2, J-B Kirschner3, N Venhoff1 and UA Walker1,4 Both zidovudine and zalcitabine induced a mitochondrial cardiomyopathy, which is antagonized by uridine supplementation. The results provide proof of the importance of pyrimidine pools in the pathogenesis of zidovudine cardiomyopathy. Because uridine supplementation is tolerated well by humans, this strategy should be investigated in clinical trials. |
| P-58 | URIDINE SUPPLEMENTATION WITH MITOCNOL ANTAGONIZES ANTIRETROVIRAL NUCLEOSIDE ANALOGUE-INDUCED MITOCHONDRIAL PERIPHERAL AND CEREBRAL NEUROPATHY IN VIVO Antiviral Therapy 2008; 13(Supp. 4):A66 (abstract no. P-58) D Lebrecht1, C Deveaud2, B Beauvoit2, J Bonnet2, J-B Kirschner3, K Müller4, N Venhoff1 and UA Walker1,5 Zidovudine and zalcitabine induce a mitochondrial peripheral and cerebral neuropathology, both of which are antagonized by Mitocnol. |
| P-59 | MITOCHONDRIAL DNA AND RNA CONTENT IN PLACENTAL TISSUE FROM HAART-TREATED HIV PREGNANCIES Antiviral Therapy 2008; 13(Supp. 4):A67 (abstract no. P-59 HCF Cote1,2, E Papp1, E Maan3, I Gadawski1, T Chaworth-Musters1,2, J van Schalkwyk1, J Forbes3, D Burdge3, A Alimenti3 and D Money1,2,3 Exposure to HAART during pregnancy appears to affect placental mitochondria differentially on the maternal than on the fetal side of the organ. This might reflect an adaptation to drug pressure. Multidrug resistance gene induction, a potentially protective mechanism, is highly comparable throughout the tissue in HAART-exposed placentae. Change in mitochondrial function might adversely affect placental metabolism and energy production, which could have serious effects on fetal organ development and function. |
| P-60 | IN VIVO EVALUATION OF THE EFFECT OF ANTIOXIDANT SUPPLEMENTATION ON MITOCHONDRIAL FUNCTION AND BODY COMPOSITION IN HIV-INFECTED PATIENTS WITH LIPOATROPHY Antiviral Therapy 2008; 13(Supp. 4):A68 (abstract no. P-60) L Milazzo1, B Menzaghi1, M Nasi2, I Caramma1, B Zanone-Poma1, M Iannuccelli3, A Cossarizza2 and M Galli1 In HIV-associated lipoatrophy, dietary supplementation with carnitine or lipoic acid/Nacetylcisteine for 12 months significantly improved mt function, but no amelioration of fat mass distribution or lipid and glucose metabolism was obtained. |
| P-61 | EFFECT OF SUBSTITUTING TENOFOVIR FOR ZIDOVUDINE VERSUS CONTINUING ZIDOVUDINE ON PHYSIOLOGICAL CORRELATES OF MITOCHONDRIAL FUNCTION IN HIV-INFECTED SUBJECTS ON NUCLEOSIDE-REVERSE TRANSCRIPTASE INHIBITOR THERAPY Antiviral Therapy 2008; 13(Supp. 4):A68 (abstract no. P-61 G Ionescu, R Walker, JB Albu, ES Engelson and DP Kotler Despite little clinical evidence of mitochondrial dysfunction, switching led to detectable physiological changes in adipose tissue and the liver, the latter as increased lactate clearance and decreased hepatic fat content. Switching to tenofovir from zidovudine had no detectable effects on skeletal muscle as aerobic capacity, peak lactate production and glucose disposal remained unchanged. |
| P-62 | EFFECTS OF A 144-WEEK-LONG CD4-GUIDED HIV TREATMENT INTERRUPTION ON MITOCHONDRIA Antiviral Therapy 2008; 13(Supp. 4):A69 (abstract no. P-62) G Garrabou1, E Negredo2, C Moren1, J Romeu2, B Rodriguez-Santiago2,3, M Nicolàs1, Ò Miró1, F Cardellach1, J Puig2, N Pérez-Álvarez2, R López-Blánquez2, L Ruiz4, R Bellido4, C Miranda2 and B Clotet2,4 The mitochondrial function of peripheral blood mononuclear cells improved during a prolonged ARVT interruption despite mtDNA content decrease. The absence of correlation between mitochondrial parameters suggests the existence of a mitochondrial transcriptional or translational upregulation mechanism, which could be increasing mitochondrial protein expression in absence of mtDNA content improvement or could also be the reversion of an ARV-mediated mitochondrial toxicity mechanism that was previously disturbing mitochondrial function through a DNA polymerase . independent way. |
| P-63 | MITOCHONDRIAL DAMAGE INDUCED BY THE HIGHLY ACTIVE ANTIRETROVIRAL TREATMENT IN NON-HIV-INFECTED PATIENTS Antiviral Therapy 2008; 13(Supp. 4):A69 (abstract no. P-63 G Garrabou1, E Pedrol2, E Deig2, C Morén1, M Nicolàs1, P Garcia2, I Vidal2, F Cardellach1 and Ò Miró1 In non-HIV-infected patients, 1 month of ARV treatment induced mitochondrial damage, even when considering HAART consisting of FTC+TDF+SQV/r with a theoretical low mitochondrial toxic profile. Mitochondrial changes consisted of slight mtDNA depletion and moderated mtDNA-encoded MRC complex IV dysfunction, although none of these changes were statistically significant. These findings validate HAART-induced mitochondrial toxicity, even in the absence of HIV infection. Further studies should be performed to assess mitochondrial toxicity of different HAART schedules in non-infected individuals to elucidate toxic effects of ARVs without HIV or previous ARV interference. |
| P-64 | MITOCHONDRIAL DYSFUNCTION IN HIV-INFECTED CHILDREN RECEIVING OR NOT ANTIRETROVIRAL THERAPY Antiviral Therapy 2008; 13(Supp. 4):A70(abstract no. P-64) C Morén1,2, G Garrabou1,2, A Noguera3, M Nicolàs1,2, F Cardellach1,2, C Fortuny3 and Ò Miró1,2 We found a reduction in mtDNA amount in HIV-infected children with respect to healthy controls. However, this depletion was not reflected in MRC CIV activity dysfunction. HAART does not seem to interfere with mitochondrial parameters. Future studies will be performed in order to determine whether this is caused by upregulatory mechanisms or longer time is required to detect alterations in MRC. |
| P-65 | ANTIRETROVIRAL TREATMENT INTERRUPTION FOLLOWED BY AN INCREASE IN MITOCHONDRIAL DNA CONTENT IN HIV-INFECTED CHILDREN Antiviral Therapy 2008; 13(Supp. 4):A70 (abstract no. P-65 C Morén1,2, G Garrabou1,2, N Rovira3, A Noguera3, M Nicolàs1,2, F Cardellach1,2, Ò Miró1,2 and C Fortuny3 mtDNA content restoration was found in a group of perinatally HIV-infected paediatric patients after 12 months of highly active antiretroviral therapy interruption. Our results suggest that mitochondrial damage is because of the use of nucleoside analogues rather than to HIV infection itself. In this setting, it is important to investigate new therapeutic treatment-sparing strategies in HIV-infected paediatric patients. |
| P-66 | MITOCHONDRIAL TOXICITY IN HIV PATIENTS TREATED WITH ANTIRETROVIRALS MANIFESTING AS A SYNDROME RESEMBLING CHRONIC PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA Antiviral Therapy 2008; 13(Supp. 4):A71 (abstract no. P-66) G Pfeffer1, M Mezei1, CX Li1, M Jitratkosol1, JS Montaner1,2 and HCF Cote1 These cases suggest that combined mt toxicity from HIV infection and antiretroviral therapy can occasionally produce syndromes resembling mt disorders, which could improve by withdrawing the offending agent. Concurrent statin therapy might have contributed to the muscle symptoms. It is unclear whether HIV infection and mitotoxic agents can produce the syndrome on their own or whether they might exacerbate and unmask previously present subclinical mt disease. Nevertheless, the incidence of this CPEO-like syndrome, a rare disease in the general population (the prevalence of all mt diseases combined is approximately 1/8,500), seems high considering that our total patient population on HAART is approximately 4,500. The observation of CPEO-like syndrome might increase as the number of aging HIV survivors with long-term HAART exposure rises. |
| Clinical Management of ADRs |
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| P-67 | IMPACT OF BODY CHANGES ON THE QUALITY OF LIFE OF HIV-POSITIVE TREATMENT-EXPERIENCED PATIENTS – AN ONLINE COMMUNITY-BASED SURVEY Antiviral Therapy 2008; 13(Supp. 4):A73 (abstract no. P-67 N Vergel Despite the inherent limitations and possible biases of self selection and the limited survey population, body changes appear to take a major toll in the quality of life of patients. The majority of patients in this sample reported eroding self-image, increased isolation and depression/anxiety, and most associate these with drugs used in the treatment of HIV disease. The patients’ belief that there is an association with the treatment drugs they use has a negative effect on patient adherence to prescribed regimens. |
| P-68 | HEALTH-RELATED QUALITY OF LIFE IN HIV-INFECTED PATIENTS IN A PRIVATE PRACTICE IN GERMANY Antiviral Therapy 2008; 13(Supp. 4):A73 (abstract no. P-68) S Mauss, J Henke, F Berger, P Hegener and G Schmutz HIV-positive patients rate their QoL worse than healthy controls, but better than HIV-positive individuals from mid-90s. Compared with HIV-negative individuals, QoLisimpairedintheQoL-CEdomainindependentofhealth status. This suggests that being HIV-infected represents an emotional stress despite improved physical wellbeing. Effects of different drug classes should be interpreted carefully because of a potential selection bias. |
| P-69 | ECONOMIC MODELLING OF THE COMBINED EFFECTS OF HIV DISEASE, HEART DISEASE AND LIPOATROPHY BASED ON ACTG 5142 TRIAL DATA Antiviral Therapy 2008; 13(Supp. 4):A74 (abstract no. P-69 KN Simpson1, R Rajagopalan2, B Dietz3, KW Garren4, S Riddler5 and R Haubrich6 Initiating an LPV/r-containing regimen on ARV-naïve patients appears cost effective compared with an EFV-based regimen when the cost and consequences of lipoatrophy are included. |
| P-70 | COST EFFECTIVENESS AND BUDGET IMPACT OF LOPINAVIR/RITONAVIR (LPV/R) AND ATAZANAVIR PLUS RITONAVIR (ATV+RTV) REGIMENS BASED ON 48-WEEK RESULTS FROM THE CASTLE STUDY Antiviral Therapy 2008; 13(Supp. 4):A74 (abstract no. P-70) KN Simpson1, R Rajagopalan2 and B Dietz3 The use of an ATV+RTV-based regimen in ARV-naïve patients with a CHD risk similar to patients in the CASTLE study is not a cost-effective use of scarce resources. The very small added CHD risk incurred by LPV/r treatment is more than offset by its short- and long-term cost savings. |
| P-71 | COST CONSEQUENCES OF HIV-ASSOCIATED LIPOATROPHY Antiviral Therapy 2008; 13(Supp. 4):A75 (abstract no. P-71 J Hornberger1,2, R Rajagopalan3, A Shewade1 and M Loutfy4 Treatment of HIV-associated lipoatrophy may represent a considerable out-of-pocket expense for many patients with HIV and will influence the decision options and pathways. |
| P-72 | TREATMENT OF HIV-RELATED FACIAL AND BODY LIPODYSTROPHY WITH POLYMETHYLMETHACRYLATE (PMMA): 10 YEARS EXPERIENCE Antiviral Therapy 2008; 13(Supp. 4):A75 (abstract no. P-72) MS Serra1,2, LZ Gonçalves1 and SG Gontijo1 Treatment of facial and body lipoatrophy related to HIV lipodystrophy with PMMA solution demonstrated to be safe, efficient and long-lasting, with minimum side effects. The treatment had a positive influence on patients, helping them get more self confident and improving their quality of life. |
| P-73 | SURGICAL INTERVENTION PROGRAMME FOR HIV-ASSOCIATED LIPODYSTROPHY PATIENTS: EXPERIENCE OF THE HELIÓPOLIS HOSPITAL, SÃO PAULO, BRAZIL Antiviral Therapy 2008; 13(Supp. 4):A76 (abstract no. P-73 H Zambrini1,2, RS Brasileiro1, GA Scozzafave1, DJ Neto1 and JJD Furtado1 The main importance of surgical interventions in HIV-associated lipodystrophy patients lies in providing improvement in patients’ quality of live and self esteem, assuring commitment to antiretoviral treatment. This is a current reality that should be expanded to all HIV centres. |
| P-74 | FACIAL FILLING WITH POLYMETHYLMETHACRYLATE IN SÃO PAULO, BRAZIL: EXPERIENCE OF 650 PATIENTS Antiviral Therapy 2008; 13(Supp. 4):A60 (abstract no. P-74) MCN Yoshioka, S Yarak, CSL Kamamoto, DL Estevam, M Fonsi, RA Souza and MC Gianna It is very important that the government have policy statements for prevention and treatment on all aspects of HIV care. The scope of responsibility of AIDS coordination goes beyond the universal access to HAART, which has already been in place since 1996 in Brazil. We observed low incidence of complications after 3 years of filling with PMMA. |
| Developing World |
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| P-75 | PREVALENCE AND DETERMINANTS OF METABOLIC SYNDROME AMONG LATIN AMERICAN HIV-INFECTED PATIENTS ON HAART: RAPID II STUDY Antiviral Therapy 2008; 13(Supp. 4):A79 (abstract no. P-75 O Sussman1, R Salazar2, J Galidez3, F Rangel4, ML Castañeda5, G Lopardo6, CA Cuhna7, Y Roldan8, R Gutierrez9, G L’Italien9,10, N Cure-Bolt9 and M Castrillo11 for the Rapid II Study Group Metabolic syndrome is prevalent in this cohort of Latin American HIV-infected patients and it is associated with higher risk of CVD. Factors independently associated with metabolic syndrome are age, female gender, family history of CVD and CD4 cell count, but not time living with HIV and duration of HAART. |
| P-76 | METABOLIC SYNDROME AMONG PATIENTS INITIATING HAART AND OUTCOME IN SOUTHERN INDIA Antiviral Therapy 2008; 13(Supp. 4):A79 (abstract no. P-76) S Saghayam1, N Kumarasamy1, M Sundaram1, S Solomon1, G Shivaji2, K Mayer3, and C Wanke4 This study shows a high frequency of metabolic syndrome among HIV-positive patients because of low HDL and high insulin resistance. Efavirenzbased HAART, due to its beneficial effect on HDL, has been protective against metabolic syndrome in the first 12 months in this study, but its long-term effects need to be studied. As HAART is available in large-scale government programmes, routine monitoring of metabolic parameters are essential to minimize cardiovascular risk. |
| P-77 | GENDER DIFFERENCES IN METABOLIC PROFILE AND CARDIOVASCULAR RISK AMONG LATIN AMERICAN HIV-INFECTED PATIENTS ON HAART: RAPID II STUDY Antiviral Therapy 2008; 13(Supp. 4):A80 (abstract no. P-77 A La Rosa1, PRA Ferreira2, Y Roldan3, G Lopardo4, O Sussman5, M Castrillo6, J Galindez7, E Ticona8, P Mantilla9, G L’Italien9,10, N Cure-Bolt9 and DB Pedral11 for the Rapid II Study Group Baseline data from this cohort of HIV- infected Latin American adults on HAART showed an overall higher CVR in males, with higher rates of smoking, hypertension and dyslipidaemia. In contrast, obesity metabolic syndrome and lack of physical exercise were more frequent among women. Recognition of gender differences in this setting is important for appropriate intervention on modifiable CVR factors. |
| P-78 | QUALITY OF LIFE AND BODY IMAGE IN THE ASSESSMENT OF PSYCHOLOGICAL IMPACT OF FACIAL LIPOATROPHY: CONSTRUCTION AND VALIDATION OF ASSESSMENT OF FACE & BODY CHANGE AND DISTRESS QUESTIONNAIRE Antiviral Therapy 2008; 13(Supp. 4):A81 (abstract no. P-78) M Ferrara1, R Murri2, E Bertaccini3, G Orlando3, M Vandelli3, M De Paola3, B Beghetto3, V Barbanti Silva1, M Rigatelli1 and G Guaraldi3 Preliminary evidence supports the reliability and validity of the Italian version of the ABCD-F in people with HIV and F-LA. This questionnaire may be useful to identify people experiencing greater impact of F-LA, or to evaluate the impact of interventions to treat LD, such as plastic surgery. |
| P-79 | BRAZILIAN POLITICS ON LIPODYSTROPHY TREATMENT IN THE PUBLIC HEALTH SYSTEM Antiviral Therapy 2008; 13(Supp. 4):A82 (abstract no. P-79 K Abreu1, C Ferreira1, M Serra2 and M Yoshioka3 After these actions, the Brazilian Ministry of Health established a governmental decree in March of 2007 to establish the treatment for lipodystrophy in Brazilian public hospitals by offering two types of interventions: facial lipoatrophy treatment with polymethylmethacrylate (PMMA) and repairing plastic surgery for fat accumulation, especially in the belly, breasts and dorsum cervical (buffalo humps). At this moment, eight public hospitals had attempted to conform to the decree and are started with the procedures. For 2009, the objective is to have 64 public services offering 4,800 facial lipoatrophy treatment and 29 public hospitals realizing 1,600 plastic surgeries. These estimated numbers were based on the numbers of patients taking highly active antiretroviral therapy in the country, which now totals 184,000 persons, and the operative capacity of the public hospitals and health services established in the Brazilian public health system. |
| Liver Disease & Hepatotoxicity |
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| P-80 | SCREENING FOR LIVER FIBROSIS IN HIV-MONOINFECTED PATIENTS WITH INCREASED ALT COMPARING FIBROSCAN WITH FIB-4 Antiviral Therapy 2008; 13(Supp. 4):A83 (abstract no. P-80) S Mauss, J Henke, F Berger, P Hegener and G Schmutz In this ongoing study, approximately 20% of HIV-monoinfected patients had increased ALT. Advanced liver fibrosis was rare in this cohort of HIV-monoinfected individuals and there was good agreement between Fibro-Scan and FIB-4. |
| P-81 | STATISTICAL AGREEMENT BETWEEN ULTRASOUND (US) AND COMPUTERIZED TOMOGRAPHY (CT) FOR NONALCOHOLIC LIVER DISEASE (NAFLD) DIAGNOSIS Antiviral Therapy 2008; 13(Supp. 4):A83 (abstract no. P-81 C Stentarelli1, S Ballestri2, S Zona1, L Amedeo3, R D’amico4, N Squillace1, G Orlando1, P Loria2 and G Guaraldi1 Non-invasive imaging agreement between US and CT to diagnose NAFLD is less than ideal. Best concordance is found for US≥3 and L/S≤1.1. Liver biopsy studies are needed to validate cutoff of US evaluation and L/S in people living with HIV. |
| P-82 | ACUTE LIVER FAILURE ASSOCIATED WITH EFAVIRENZ-BASED HAART REQUIRING LIVER TRANSPLANTATION IN A CHILD Antiviral Therapy 2008; 13(Supp. 4):A84 (abstract no. P-82) A Turkova1, C Ball2, S Gilmour-White3, M Rela4 and G Mieli-Vergani4 Histology of the explanted native liver showed severe hepatitis with multiacinar parenchymal cell necrosis without features of mitochondrial toxicity. He had a stormy 3 months in a paediatric intensive care unit and required 2 liver transplants. Having excluded all common causes of ALF, it is possible that the severe liver injury in our patient was related to ART. Nucleoside reverse transcriptase inhibitors are unlikely to be involved as there was no increased lactate or evidence of mitochondrial toxicity on liver histology. Efavirenz, however, may be implicated. |
| P-83 | CLINICAL PRESENTATION OF HEPATOCELLULAR CARCINOMA (HCC) IN HIV-INFECTED PATIENTS Antiviral Therapy 2008; 13(Supp. 4):A85 (abstract no. P-83 I Poizot-Martin1, O Faucher1, L Dahan2, P Ries2, S Benhaim1, M-P Drogoul-Vey1, A Menard1, S Bregigeon1 and J-F Seitz2 The number of HCC cases in our clinical database has increased since 2001. In most cases, HCC has been detected at advanced stages with a poor survival and, in one case, in a patient with a long-term SVR after anti-HCV therapy. These results argue for a prospective detection of HCC in HIV–HCV-coinfected patients, which should concern not only patients with cirrhosis and also patients with SVR after anti-HCV therapy. |
| Renal Toxicities |
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| P-84 | TENOFOVIR AFFECTS KIDNEY mtDNA AND CELLULAR ENERGETIC HOMEOSTASIS Antiviral Therapy 2008; 13(Supp. 4):A87 (abstract no. P-84) M Stankov, RE Schmidt, GMN Behrens and the German Competence Network HIV/AIDS In our mouse model, long-term TDF treatment was able to deplete mtDNA in the kidney and to disturb the cellular energetic status of cells this organ. |
| P-85 | EVALUATION OF RENAL SAFETY FOR LOPINAVIR/RITONAVIR (LPV/R) TABLETS DOSED ONCE DAILY (QD) OR TWICE DAILY (BID) ADMINISTERED WITH TENOFOVIR DISOPROXIL FUMARATE (TDF) AND EMTRICITABINE (FTC) IN ANTIRETROVIRAL-NAÏVE (ARV) SUBJECTS: RESULTS FROM STUDY M05-730 Antiviral Therapy 2008; 13(Supp. 4):A87 (abstract no. P-85 BA da Silva, D Cohen, S Gibbs, L Fredrick and B Bernstein Renal dysfunction was an infrequent complication of therapy and rarely resulted in TDF interruption or discontinuation. Changes were similar or less than those previously reported in literature. Lower baseline CrCl, higher age and lower body mass index were predictive of decreased CrCl at week 48. |
| Other Toxicities |
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| P-86 | ADRENOCORTISOL SUPPRESSION INDUCED BY THE INTERACTION BETWEEN RITONAVIR AND DIFFERENT INHALED CORTICOSTEROIDS Antiviral Therapy 2008; 13(Supp. 4):A89 (abstract no. P-86) R Andrianasolo, M Blanc, D Durand and P Leclercq Adrenal suppression is a common event in patients treated by inhaled corticosteroids and baby-dose ritonavir and might be undiagnosed if not routinely monitored. Even in a prospective study, we found profound adrenal insufficiency needing systemic supplementation. Fluticasone was already known for this interaction, but budesonide was also of concern. |
| P-87 | DIAGNOSIS AND TREATMENT OF RITONAVIR (RTV)-INDUCED IATROGENIC CUSHING SYNDROME WITH SECONDARY ADRENAL INSUFFICIENCY IN AN HIV-INFECTED ADULT RECEIVING INHALED FLUTICASONE Antiviral Therapy 2008; 13(Supp. 4):A89 (abstract no. P-87 E Hayashi, H Abe, S Imamura and A Hirai Practitioners should be aware of the effect of coadministration of PI-based ART regimens with inhaled corticosteroids on the adrenal axis. Further, pharmacokinetic study with a detailed analysis of the FP level in blood samples and measurement of the morning ACTH and cortisol levels greatly contributed to hormone replacement therapy leading to successful recovery from adrenal insufficiency. |
| P-88 | AGE-RELATED COMORBIDITIES IN PEOPLE LIVING WITH HIV Antiviral Therapy 2008; 13(Supp. 4):A90 (abstract no. P-88) G Guaraldi1, S Zona1, G Orlando1, N Squillace1, C Stentarelli1, G Nardini1, B Beghetto1, R Esposito1 and F Palella2 Metabolic, cardiovascular endocrine, hepatic and kidney disease are age-associated conditions highly prevalent in people living with HIV. Multiple comorbidities increase with age and witness the multidisciplinary care needs of HIV aging population. |
| P-89 | MEASURING GASTROINTESTINAL ADVERSE EVENTS IN CLINICAL TRIALS Antiviral Therapy 2008; 13(Supp. 4):A90 (abstract no. P-89 A Hill1,2, M Prakash2 and C Moecklinghoff2 Several different endpoints have been used to assess GI AE in HIV clinical trials. Most GI AEs were grade 1 and judged unrelated to study medication. The use of a standardized endpoint appears to lead to similar rates of GI AE’s across similar trials of a standard treatment and consistent differences within the PI class. |
| P-90 | GENDER DIFFERENCES IN DEPRESSION EVOLUTION IN A COHORT OF PATIENTS ATTENDING A METABOLIC CLINIC FOR LIPODYSTROPHY MANAGEMENT Antiviral Therapy 2008; 13(Supp. 4):A91 (abstract no. P-90) G Orlando, N Squillace, B Beghetto, G Nardini, I Mazeu and G Guaraldi As demonstrated in the general population, women with HIV infection seem to be more vulnerable than men to experiencing more severe depression symptoms that still remain even after face lipoatrophy treatment. This issue underlines the need for new studies analysing the gender peculiarity of depression among patients with HIV infection. |
| P-91 | BODY IMAGE IS A MAJOR DETERMINANT OF SEXUAL DYSFUNCTION IN STABLE HIV-INFECTED WOMEN Antiviral Therapy 2008; 13(Supp. 4):A92 (abstract no. P-91 K Luzi1, G Guaraldi1, R Murri2, M De Paola1, G Orlando1, N Squillace1, R Esposito1, R Vincenzo1, L Zirilli1 and E Martinez3 D was highly prevalent in this cohort. Self-perceived body changes were identified as its major determinant. |
| P-92 | MEASUREMENT OF 3-METHYLHISTIDINE IN SPOT URINE FROM HIV-INFECTED PERSONS: AN ALTERNATIVE SCREENING METHOD FOR MUSCLE PROTEIN DEGRADATION TO SERUM CK? Antiviral Therapy 2008; 13(Supp. 4):A92 (abstract no. P-92) AC Venhoff1, E Bissé2, T Epting2, J Thoden1, D Lebrecht1, UA Walker1 and N Venhoff1 In conclusion, measurement of 3-MH on spot urine samples is not useful for assessing changes in muscular protein degradation. A meat-free diet, 24 h urine collection and refraining from physical activity might reduce confounding factors of 3-MH secretion. |
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