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Session 21
Symposium Controversies in Antiretroviral Therapy Session Time: Tuesday, 7 - 9 pm Room 4B |
Background: Highly active antiretroviral therapies (HAART) lower mobility and mortality of HIV infection, but are unable to eradicate HIV and may cause side-effects. Strategic (also called planned or structured) treatment interruptions are studied for 3 reasons: to stimulate the anti-HIV immune response after viremia has been suppressed by treatment (autovaccination), to increase time off drug, in order to improve quality of life and diminish side effects, as well as costs, and, among individuals whose virus has become resistant to treatment, to induce reversion of resistance to wild-type and therefore to improve the success of subsequent salvage therapy. Regarding autovaccination, the most promising results come from the rare patients who started HAART during primary HIV infection. Up to 60% have controlled viremia below 5000 copies/mL, for up to 1 year without HAART. In vitro, there is evidence for enhancement of CD4- and CD8-cell HIV-specific immune response. In the majority of patients who started HAART later, 17% (CI 11-25 %) of patients remained with a viremia <5000 after 4 off-on cycles (2 weeks on, 8 weeks off) followed by 12 weeks’ treatment interruption. In vitro tests also show stimulation of HIV-specific cytotoxic lymphocyte responses (CTL). However, such stimulation did not predict a state of low viremia without therapy; to the contrary, patients with higher rebounds tended to have more active CTL. In this population, additional immune stimulatory manoeuvres are being planned, such as administration of cytokines, or specific immune treatment by anti-HIV vaccines (therapeutic vaccination). Conclusions: Intermittent HIV therapies also hold out the promise of fewer side effects, and of a more favourable cost/benefit ratio for HAART; in this, they are particularly interesting for developing countries. Risks (such as selection of resistant quasispecies and increase in HIV infectiousness during rebounds) and benefits still have to be compared in large clinical trials which are currently in the planning stage. Many types of treatment interruptions are being planned: Long interruptions. Start and stop of treatment may be guided by the calendar (e.g., 2 months on, 2 months off), or by the CD4 count (e.g., suspend treatment each time the CD4 count >350/(L). Rebounds of viremia and falls in CD4 counts are to be expected. Short interruptions. A pilot study has shown that in patients treated with ritonavir-boosted indinavir, stavudine, and lamivudine, no rebounds were observed on a schedule of 1 week on, and 1 week off therapy. Potential advantages to this approach are steady CD4 cell counts, and lesser contagiousness. When treatment is interrupted in patients who fail HAART and who have drug-resistant HIV, the drug-sensitive wild-type replaces the resistant quasi-species in 30-60%. In a recently completed randomized study, the viral load response to salvage therapy with 6-9 drugs was better in patients who were randomized to a drug holiday before salvage. However, the drop in CD4 counts during treatment interruption is of concern, as these patients are often immunosuppressed and therefore vulnerable to opportunistic infections. |
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©2002 9th Conference on Retroviruses and Opportunistic Infections |
