IAPAC Monthly - Vol. 8, No. 4, April 2002
Mike Youle

9th Conference On Retroviruses and Opportunistic Infections, February 24 - 28, 2002 – Seattle

In his seminal work, A Brief History of Time, Cambridge University theoretical physicist Stephen Hawking examines the relationship between space and time with regard to the universe. At one point, he describes the thermodynamic arrow of time that relates to the Second Law of Thermodynamics. The latter states that in any closed system disorder increases with time, a form of Murphy’s law (read: things always seem to go wrong). Hawking goes on to relate the thermodynamic arrow of time to the psychological arrow of time (in that we remember the past but not the future) and the cosmological arrow of time, which states that the universe is expanding. These ideas are used to explain or attempt to evaluate the relationship between time and motion. Hawking concludes that human beings can only exist in an expanding universe. We expend more energy than we create to exist. Indeed, the mere reading of this article in the IAPAC Monthly will use up far more energy in living than you can ever conserve by the creation of order in your brain.

There is a fascinating cyclical, but ultimately progressive direction that appears to exist in science and clinical medicine. We approach each new area of interest by forays into unknown territory followed by returns to a more normative stance, a pendulum of advancement. The tides of HIV research are like waves on a beach with the occasional high tide that changes the topography forever. What we witnessed at the 9th Conference on Retroviruses and Opportunistic Infections (CROI), held February 24-28, 2002, in Seattle, was yet another backwash of information that increased our knowledge in some of the multifarious areas pertaining to HIV and associated conditions while leaving others static with no obvious advances.

This article focuses partially on the dilemma of how to treat without the need to deliver continuous suppression of HIV, which, with current therapies, ultimately results in some treatment-related toxicity. As physicians are taught, primum no nocere (first, do no harm), so the potential for therapy breaks or the use of immune enhancement is always greeted with enthusiasm—although, until recently, these therapy breaks had not been backed up by hard evidence of utility. However, first we go to the 9th CROI’s opening ceremony and the stage setting for a variety of perspectives on the epidemic and its impact.

Beatrice Hahn (University of Alabama, Birmingham) first made reference to the association of this once quiet West Coast city with the booming software industry. When her slides appeared rather hesitantly, she remarked that her sin was to use a Mac computer—considered a sin because Seattle is largely non-Mac country. In delivering the Bernard Fields Memorial Lecture, she eloquently updated her previous presentations on the human zoonotic risk from the SIV reservoir. ¹ Like an orator of old, Hahn declared we were "in for a journey Back to the Future," and over the next 30 minutes told her story: 30 primate species that harbor retroviruses, at least 10 separate cross-species transmissions into humans, and the potential of course of further new transmissions.

For another exquisite description of this area, and of the impact HIV has on the potential pathogenicity of other organisms, one need only refer to articles by Robin Weiss (University College, London) and colleagues.² She had recently, with a large group of collaborators, shown that where there is a will there is a way. First, Weiss’s work revealed from captured animals and bushmeat (killed wild animals for the meat trade) that between 5 percent and 40 percent of West African animals were infected with a range of different simian retroviruses (SIV), with older animals more likely to be infected—suggesting sexual transmission. She then moved her focus to examining the chimpanzee populations that existed in the wild to establish if there was a reservoir within this species.

Her co-worker Mario Santiago (University of Alabama, Birmingham) developed non-invasive methods to evaluate the rate of infection in the wild by collection and examination of feces and urine by a remarkable set of co-workers in the bush of several African countries. When these biological samples were evaluated using an RT-PCR method to detect virus, only a very few animals could be found in the wild in which there was evidence of SIV infection. Weiss surmised that the spread of these viruses had occurred in the last 1,000 years from West Africa from a variety of monkey hosts into the chimpanzee population at several time-points and thence into man, although the epidemiology suggested that cross species transmission was a rare event. We await the sequel to this story since it is likely that since at least some animals appear to be able to live in harmony with HIV there are some answers hidden here that may allow us to do the same.

Next came a strangely emotive piece by journalist and photographer Andrew Petkin (Humanitarian Endeavors, Southlake, Texas), which one must assume was designed for those who do not work at the coalface of HIV. He showed numerous pictures of the heartache of HIV/AIDS, in Africa specifically, with barely a mention of the rest of the world. He used descriptions such as the "tidal wave—leaving in its wake a perverse population of orphans and old people" and observations such as "statistics are merely people with the tears removed." This and other text helped to create a number of images of the horror and scale of the African epidemic.

However, in the cathedral-like environment of the Washington State Convention and Trade Center, his presentation strangely evoked theological aspects of the crucifixion being discussed 2,000 years later, an academic observation of a human trauma. Perhaps Petkin’s words did help those delegates who have had little contact with the everyday uncertainty and fears of HIV. And, undoubtedly, the presentation did reveal the problems of Africa as a melange of social, anthropological, economic, and above all political issues which medicine and science alone cannot turn around.

Finally, it was the turn of computer magnate turned philanthropist Bill Gates to discuss the "Role of Philanthropy in Fighting AIDS and Improving Global Health." After describing what we may have in the way of high tech tools for the next few years (at least from his Microsoft Corp.), Gates went on to explain how his business philosophy has drawn him to help and support health-related projects in a number of areas, including AIDS.

While understanding his willingness and eagerness to rapidly change the terrible circumstances under which billions of people live worldwide, it was also clear that Gates understood, to a degree, that money for HIV/AIDS care alone is not helpful. Supporting research in the underlying science is also required to create the huge advances that have already been made and need to be made if we are to avoid being engulfed by this and the next wave of epidemics "designed" to reduce the human population.

It was fitting that the first two plenary talks at the 9th CROI dealt with different aspects of the immune system and how they may play a role in HIV entering the body and in its control once there. Melissa Pope (Population Council, New York) gave a clear explanation of the types and roles of dendritic cells that play a vital role in the orchestration of the immune response to external antigen (foreign material).³ These cells take up antigen and then move it around the body and present it to the body for recognition and destruction.

With HIV, these cells act as a "Trojan Horse," allowing HIV to gain access to the very heart of the immune system. Since this process is vital for the spread of HIV away from the local infection site, it is a potential target for development of anti-HIV agents to prevent this process. Microbicides would be potential agents to block the interplay between dendritic cells and HIV and thereby limit the incursion of the virus into the body. Of course as yet it is unclear to what degree this is the major route of entry of the virus.

Brigitte Autran (Hôpital Pitié- Salpétrière, Paris) then took up the mantle of explaining the action of the immune system to attempt to control the damage HIV causes and the opportunities that are afforded by the use of highly active antiretroviral medication.⁴ She noted "the powerful capacity of antiretrovirals to reconstitute the immune system." The major dilemma occurs from the fact that during primary HIV infection cytotoxic T-lymphocytes (CTLs) recognize cells that are actively producing HIV and target them for attack whereas later in infection this capacity is lost. Tests such as the EliSpot show that these HIV-specific CTLs are present in low numbers since there is a decrease in antigen and perhaps defective dendritic cell activity due to the effectiveness of HIV treatment.

Autran noted that treatment interruptions are problematic in that they cause rapid antigen exposure but also result in a viral load rise that causes total CD4 cell decline. Therefore, her conclusion was that therapeutic vaccination was likely to hold out some degree of hope to allow immune reconstitution to maximally occur with HIV-specific cells as a large proportion of the response. Then and only then, Autran suggested, is it possible that interruption of treatment would result in a sustained low viral load and prolongation of good health.

In terms of primary HIV infection, following from the work of Eric Rosenberg (Massachusetts General Hospital, Boston) et al, the early results of the PRIMSTOP pilot trial (ANRS 100) show some promise.⁵ In this multicenter prospective trial, 29 subjects at an early stage after seroconversion were treated with a combination of stavudine, didanosine, nelfinavir and hydroxyurea for approximately nine months, followed by a series of treatment interruptions at three monthly intervals, which increase, from two weeks to four weeks and then to six weeks. Although the patients were later in their infection than those studied by Rosenberg, the outcomes seemed to indicate in the first group of 12 subjects to have had three breaks that eight subjects had controlled virus to a load <10,000copies/mL and five subjects were below 1,000 copies/mL. Whether this was due to the use of hydroxyurea alone, which limits target cell activation in HIV, or hydroxyurea combined with the treatment interruptions is uncertain. However, if these results could be replicated in a randomized controlled study a new treatment modality would be available for those few individuals who are seen at the time of seroconversion.

Further along in HIV disease from initial infection treatment interruption, stopping therapy pro-term and fixed period intermittent on-off therapy schedules have all been proposed, discussed and to some degree studied over the past couple of years. A number of "facts" about these strategies are clear, much more is less so. When treatment is stopped viral load rebounds usually to around the pre-treatment level, and over the next few months CD4 cell counts decline at a variable rate that appears to have little predictability. Some small studies (none randomized) have hinted that this strategy is more successful in those people who were treated at seroconversion, and that the further along in HIV disease you go the more risky will be interrupting therapy that has suppressed HIV.

Tantalizing data, first shown at the 8th European Conference on Clinical Aspects and Therapy in HIV (October 2002, Athens), appeared in the Giga-HAART study, from Christine Katlama (Hôpital Pitié-Salpétrière, Paris) and her group. This was the first controlled data to build on work by the Royal Free Hospital group in London, that of Steve Deeks (University of California, San Francisco), and of Veronica Miller (formerly of JW Goethe Institut, Universität, Frankfurt) showing that potential benefits existed in shortterm treatment interruptions in salvage patients who then recommenced a new regimen.

Thus, the 9th CROI was a forum for synthesizing new data into the idea that interruption of antiviral suppression may be a double-edged sword. What you gain by lower toxicity and lack of pills may be offset by physical and laboratory changes showing that HIV was once more attacking the immune system. Of course, the fundamental question remains: do you gain any delay in disease progression by treatment that is not available if you delay treatment until the risk of disease occurrence is higher?

The "treat now, or treat later" discussion is intricately linked to the question of treatment interruption. In addition, there is now a large clinical endpoint study called Optima that will examine 1,300 patients who are three-drug class failures and who will be randomized to have a 3- to 6-month treatment interruption versus immediate switch to a salvage regimen. These patients will also be randomized to take a standard three-drug optimized HAART regimen or a Mega-HAART five or more drug regimen. This trial, which is now open to recruitment in the United States (through Veterans Affairs hospitals), across Canada, and the United Kingdom, should provide some more definitive answer as to the utility of this approach in later stage disease.

Overall, there were 26 presentations on this topic at the 9th CROI, including two late-breakers. They fell into a number of subject groups. The first were those that examined the effects on the viral populations and immune function in different tissues when treatment was ceased. Andrew Leigh Brown (University of Edinburgh, Scotland) worked with a group from the University of California, San Diego, led by R. J. Ellis, to examine the dynamics of viral rebound in the cerebrospinal fluid (CSF).^6,7 In two of nine patients studied where sufficient data points were available (understandably, repeat lumbar punctures are not popular with patients), there was a difference between CSF and plasma viral kinetics. A rise in white cells (pleocytosis) in four subjects was seen following the viral burst in the CSF suggesting that this is a response rather than a cause of viral turnover in the central nervous system. This work also appears to shed light on the issue that reducing viraemia systemically may limit the entry of lymphocytes and linked virus into the CSF.

Further work to evaluate the source of virus when treatment is suspended came from the group of Lydia Ruiz and J. Martinez-Picardo (irisCaixa Foundation, Badalona, Spain). They extensively examined the env sequences for 12 subjects over up to four sequential structured treatment interruptions (SSTI).⁸ Genetic analysis was performed for stretches of the genome for the envelope of the virus in DNA, plasma RNA and PBMCs. In some patients there was little shift in the genetic structure of emerging populations whilst in others there was a marked alteration. This may limit the ability of treatment interruptions to strengthen the HIV-specific cell-mediated immune responses since the exposed viral antigens keep changing during each SSTI. A single subject was more extensively studied and examination of plasma samples revealed that the HIV populations that emerged over successive interruptions probably reflect a combination of reactivation of archived populations and ongoing selection due to the effect of cytotoxic T-lymphocyte responses.⁹

The role of neutralizing antibodies in treatment interruptions was examined by a group of investigators working on the Swiss Spanish Intermittent Therapy Trial, where subjects had four cycles of two weeks off/eight weeks on therapy.¹⁰ In 10 subjects at week 2 and 25 subjects after week 42, virus was isolated from PBMCs and examined for replicative capacity and for neutralizing antibodies. Although neutralizing antibody levels did not increase over the cycles of the study during the 4-6 treatment free period, after the 4 cycles there was a significant increase in these antibodies (90 percent inhibition titre >1/1000). This occurred especially in the subgroup of subjects who had maintained control of viremia throughout the study.

Next were those studies that evaluated the effects of treatment interruption on the progression of disease in prospective studies. The largest of these came from the EuroSIDA cohort that represents large clinical centers across Europe and is a long established study that has been prospectively followed for many years.¹¹ Jens Lundgren (D:A:D Coordinating Center, Copenhagen) presented data on 565 (16 percent) subjects who interrupted therapy in a cohort of 3,610 representing 7,328 person years of follow-up after commencing HAART. Median CD4 cell count at interruption and nadir were 242/µL and 130/µL respectively. Of these patients, 290 developed new AIDS-defining illnesses or died during follow-up and 45 percent restarted treatment. In subjects with the latest T4<200/µL there were 25 clinical events in 48 person years (0.52 per PY) whereas in those with a latest T4>200/µL there were three events in 92 person-years (0.03 per PY). This suggests that absolute risk of illness still depends highly on the T4 level to which patients sink.

F. Lampe and co-workers (Royal Free Hospital Clinic, London) followed all 237 patients from their clinic who were naïve to antiretrovirals when they started a HAART regimen and who reached a viral load <400 copies/mL (within 32 weeks) or who reached a viral load <50 copies/ml without viral rebound.¹² Twenty-one percent of subjects were female; main HIV exposures were homosexual (60 percent) and heterosexual (34 percent) sex. The median age at start of HAART was 35 years. HAART was started on a median date of December 1998 (IQR September 1996 - November 2000). Baseline median (IQR) viral load was 5.3 (4.8–5.7) log copies/mL and CD4 count 193 (75–302)/mm³. Nucleoside drugs in the initial regimen were zidovudine/lamivudine 126 (53 percent), stavudine/lamivudine 76 (32 percent) and other 35 (15 percent). Other drugs were nevirapine 58 (25 percent), efavirenz 44 (19 percent), indinavir 56 (24 percent), ritonavir 21 (9 percent), nelfinavir 50 (21 percent), and ritonavir boosted protease inhibitor 29 (12 percent).

Median time from start of HAART to first measured value of 50 copies/ml was 180 days; with 1,342 viral load measures made over a total 347 person-years of follow-up after the first viral load <50 copies/ml—a median of one measure per 13.5 weeks (median over all patients of 3.8 per year). Maximum follow-up was 4.4 years. Overall 13 people (5.4 percent) experienced viral rebound (breakthrough) on therapy (rate 0.037 per person-year) representing one person with viral rebound per 26.7 person-years of follow-up. There was a (non-significant) trend towards lower rebound rate with increasing time from start of HAART.

The Badalona group also presented a prospective study. Subjects with multiple exposure to antiretrovirals were randomized to a three-month treatment interruption or an immediate switch to a new salvage regimen that consisted of lopinavir/ritonavir plus saquinavir softgel, lamivudine, didanosine and abacavir. ¹³ In the 22 subjects who had the treatment interruption (Group A), 13 (64 percent) showed a reversion to wild-type virus during this period, perhaps raising the question as to whether the period off treatment was long enough. The outcomes, in this group, were compared to the 24 subjects from Group B who had an immediate switch to the salvage regimen. They showed no significant differences although a trend was seen to better response in Group A with a CD4 cell rise of 144 compared to 80 cells/µL and a viral load drop to less than detectable level in 47 percent compared to 36 percent in Group B.

Longer-term follow-up in greater numbers of patients may however be required to show such differences. The other major Catalan research group of José Gatell (Hospital Clinic-IDIBAPS, University of Barcelona, Spain) evaluated the use of mycophenalate mofetil (MMF) and the cytostatic drug hydroxyurea in groups of patients who had started HAART close to seroconversion.^14,15 These were small studies, 15 and 20 patients, respectively, but they did show that blunting of viral load rebound occurred under both agents that appeared not to be related to decrease in cell turnover or from increase in apoptosis. Further larger studies would be valuable for each of these agents, perhaps combined with another approach.

Therapeutic vaccination to maintain the benefits accrued during antiretroviral therapy has become an area of intense interest with several studies currently reaching a degree of fruition. For instance, the Quest study is currently evaluating the utility of a Canarypox vaccine, Remune, or both prior to cessation of HAART in subjects who have been treated just after seroconversion. The group of Franco Lori and Juliana Lisziewicz (RIGHT, Washington, DC) presented data evaluating the utility of a novel topical DNA immunization (DermaVir) in preventing viral rebound during treatment interruptions in macaques.¹⁶ Ten animals with late-stage AIDS were studied and randomized to continuous HAART, STI-HAART (three weeks on, three weeks off) and after six cycles were also given DermaVir (a composition of HIV DNA plus Langerhans cell stimulant called polyethyleniminemannose designed to stimulate recognition of the DNA by the animals’ immune system). All the macaques on HAART alone were dead by month seven whereas only one on STI-HAART had succumbed. Of the three monkeys who were then treated with DermaVir, median viral load decrease during each subsequent interruption occurred until control at <200copies/mL was achieved. Clearly if this outcome were possible to replicate in humans it would be highly significant and could open the door to combination HAART and immunotherapy combination studies.

Other studies also seemed to suggest this trend with different vaccinations. A US National Institutes of Health (NIH) study using NYVAC-SIV in macaques showed similar blunting of viral rebound in immunized animals versus controls. ¹⁷ A pilot study nested within a Remune protocol evaluated the rise in viral RNA in subjects who stopped therapy for six weeks after suppressing to undetectable for at least six months.¹⁸ In the 20 Remune patients, the slope of the rise was 0.16 log10 copies/mL versus 0.21 in the eight control subjects who were only treated with the adjuvant IFA (p<0.05). The difference in the post interruption viral load level between the groups was not significant but the numbers of patients in the study precluded this being properly evaluated.

So many approaches are being currently undertaken, or are planned, to the "Treatment Interruption" scenario, using HAART, immunotherapy, cytostatic treatments and immune enhancing agents. This once again suggests that a combination of different interventions may be the best way to continue to support the inherent immune response to HIV. Only the future will tell us if we are traveling toward a more effective period of HIV treatment. What is clear is that as entropy increases so the HIV epidemic appears to be little affected as yet by the therapeutic interventions that we have and even now it continues to threaten the very global infrastructure, a fact clearly not understood by many.

Mike Youle is Director of HIV Clinical Research at Royal Free Centre for HIV Medicine in London, and a Trustee of the International Association of Physicians in AIDS Care.

References

1. Hahn BH. SIV reservoirs and human zoonotic risk. 9th Conference on Retroviruses and Opportunistic Infections. February 24-28, 2002. Seattle. Abstract L1.

2. Weiss RA. Gulliver’s Travels in HIVland. Nature 2001 Apr 19;410(6831):963-7.

3. Pope M. Dendritic cell responses and host interactions. 9th Conference on Retroviruses and Opportunistic Infections. February 24-28, 2002. Seattle. Abstract L2.

4. Autran B. Immune reconstitution and immunologic responses to antiretroviral therapies: implications for therapeutic strategies. 9th Conference on Retroviruses and Opportunistic Infections. February 24-28, 2002. Seattle. Abstract L3.

5. Hoen B, Burgard M, Fournier I, Lacabaratz C, Raffi F, Lafaurie M, Livrozet JM, Rouzioux C, Venet A, Aboulker JP, and the PRIMSTOP Study Team. Structured treatment interruptions (STI) in acute seroconverters: interim results of the multicenter prospective PRIMSTOP Pilot Trial (ANRS 100).9th Conference on Retroviruses and Opportunistic Infections. February 24-28, 2002. Seattle. Abstract 530-M.

6. Ellis RJ, Letendre SL, Frost SDW, Leigh Brown AJ, Childers ME, McCutchan JA, and HIV Neurobehavioral Research Center. Dynamics of HIV rebound in cerebrospinal fluid (CSF) after interruption of antiretroviral therapy (ART). 9th Conference on Retroviruses and Opportunistic Infections. February 24-28, 2002. Seattle. Abstract 49.

7. Price RW, Nilsson A, Deeks SG, Verotta D, and Grant R. Relationship of cerebrospinal fluid (CSF) white blood cells (WBCs) to CSF and systemic HIV infection: cross-sectional and longitudinal analysis. 9th Conference on Retroviruses and Opportunistic Infections. February 24-28, 2002. Seattle. Abstract 62.

8. Martinez-Picado J, Frost S, Marfil S, Puig T, Clotet B, and Ruiz L. Viral populations emerging in plasma during sequential structured treatment interruptions in chronically HIV-infected individuals are genetically distinct between time-points and tissues. 9th Conference on Retroviruses and Opportunistic Infections. February 24-28, 2002. Seattle. Abstract 50.

9. Joos B, Fischer M, Trkola A, Böni J, Kuster H, Oxenius A, Wong J, Phillips R, Hirschel B, Weber R, and Günthard H. Long-term multicompartment evolutionary study of HIV-env in a chronically HIV-infected patient before and during HAART followed by five structured treatment interruptions (STI). 9th Conference on Retroviruses and Opportunistic Infections. February 24-28, 2002. Seattle. Abstract 531-M.

10. Trkola A, Kuster H, Ruprecht C, Leemann C, Rusert P, Weber R, Hirschel B, and Günthard H for the Swiss HIV Cohort Study. The role of patient virus properties and neutralizing antibody responses in structured treatment interruption therapy. 9th Conference on Retroviruses and Opportunistic Infections. February 24-28, 2002. Seattle. Abstract 243-T.

11. Lundgren JD, Vella S, Paddam L, Blaxhult A, Vetter N, Clumeck N, Panos G, Fisher M, Katlama C, and Phillips AN. Interruption/stopping antiretroviral therapy and the risk of clinical disease: results from the EuroSIDA Study. 9th Conference on Retroviruses and Opportunistic Infections. February 24-28, 2002. Seattle. Abstract 48.

12. Lampe F, Johnson MA, Loveday C, Youle M, Ransom D, Sabin C, Tyrer M, and Phillips AN. Viral rebound after suppression with HAART: experience from 237 people with viral load <50 copies/mL followed for up to 4.4 years. 9th Conference on Retroviruses and Opportunistic Infections. February 24-28, 2002. Seattle. Abstract 536-M.

13. Ruiz L, Ribera E, Bonjoch1 A, Martinez-Picado J, Díaz M, Romeu J, Marfil S, Negredo E, García-Prado J, Tural C, Puig1 T, Sirera G, and Clotet B. Virological and immunological benefit of a salvage therapy that includes Kaletra plus Fortovase preceded or not by antiretroviral therapy interruption (TI) in advanced HIV-infected patients (6- month follow-up). 9th Conference on Retroviruses and Opportunistic Infections. February 24-28, 2002. Seattle. Abstract 421-W.

14. García F, Plana M, Brunet M, Arnedo M, Alcami J, Lopez-Galindez C, Tenner-Racz K, Gil C, Vidal E, Mestre G, Martorell J, Cruceta A, Miró J, Pumarola T, Gallart T, Racz P, and Gatell JM. Effect of associating an immunosuppressive therapy (Mycophenolate Mofetil: MMF) + HAART during STI and holding the MMF drug after definitive interruption of HAART on viral replication. 9th Conference on Retroviruses and Opportunistic Infections. February 24-28, 2002. Seattle. Abstract 534-M.

15. Plana M, Lopalco L, García F, Ortiz GM, Maleno MJ, García A, Arostegui J, Miró J, Nixon DF, Gil C, Cruceta A, Arnedo M, Pumarola T, Alcami J, Lori F, Gallart T, and Gatell JM. Effect of associating a cytostatic drug + HAART and holding the cytostatic drug after STI and a definitive interruption of HAART on HIV-1-specific immune responses. 9th Conference on Retroviruses and Opportunistic Infections. February 24-28, 2002. Seattle. Abstract 535-M.

16. Lisziewicz J, Xu J, Trocio J, Whitman L, Lewis MG, and Lori F. Control of viral load rebound during treatment interruptions in Macaques with AIDS induced by a novel topical DNA immunization (DermaVir). 9th Conference on Retroviruses and Opportunistic Infections. February 24-28, 2002. Seattle. Abstract 312-W.

17. Tryniszewska E, Lewis MG, Hel Z, Nacsa J, Tsai W-P, Stevceva L, Parks RW, Moniuszko M, Cairns S, Smith KA, Tartaglia J, and Franchini G. Containment of viral rebound after antiretroviral therapy suspension in Macaques chronically infected with SIV following vaccination with NYVAC-SIV recombinant vaccines. 9th Conference on Retroviruses and Opportunistic Infections. February 24-28, 2002. Seattle. Abstract 313-W.

18. Bucy RP, Moss R, and Gersten M for the 06A Study Team. Therapeutic immunization with Remune alters kinetics of viral rebound after analytical therapy interruption (ATI). 9th Conference on Retroviruses and Opportunistic Infections. February 24-28, 2002. Seattle. Abstract 314-W.

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