Sixth International Congress Drug Therapy in HIV Infection 17-21 November, 2002 Glasgow, UK

Although continuous HAART has resulted in a decrease in the mortality and morbidity rates associated with HIV infection in western countries, the utility of therapy is dampened by suboptimal activity, excess in toxicity, and inconvenience. Among 667 untreated patients from the Swiss HIV cohort, 126 had discontinued therapy as a consequence of treatment limitations. Much attention has been given, recently, to study the consequences of planned (strategic) treatment interruptions (STIs) for enhancing the utility of therapy in different settings. STIs have been studied in patients with undetectable viral load with the objective to enhance HIV-specific immunity (thereby allowing prolonged withdrawal of therapy) or to spare therapy without altering treatment activity, and in patients with multiple virologic failures with the objective of reverting multi-resistant virus to wild-type drugsensitive (with the hope of enhancing the activity of subsequent salvage therapy). Results from 14 patients, treated during acute infection and having prolonged undetectable viremia under therapy, have shown that a spontaneous control of viremia at a level not requiring therapy could be obtained in several cases following few off-therapy cycles of 3 weeks or more. Control of viremia was associated with an enhancement in HIV-specific cellular immune responses. In patients starting therapy during chronic infection, randomized studies have shown that control of viremia is infrequent when treatment is withdrawn following several cycles of STIs of 2 weeks or more. However, preliminary results obtained following shorter 7 days on/off therapy consecutive cycles in chronic patients with treatment controlled viremia, suggest that such strategy results in sparing 50% cumulative therapy without altering the effect on CD4+ counts and plasma viral load. In patients with multiple virologic failures and multi-resistant virus, an interruption in failing therapy is often followed by an apparent reversion of the virus to wild-type, although resistant virus is still present in plasma as a minor species. Some cohort studies have suggested that salvage therapy is more active (at least in the short term) when initiated following STI, but randomized studies have yielded conflicting results. However, clinical progression has been reported during STI in some patients in this setting, associated with a decrease in CD4+ counts of 100 cells/mm³ or more.

The population(s) of patients having the best benefit from STIs still remains incompletely defined. In addition, the advantages of STIs are not yet well balanced with potential risks (such as acute retroviral syndrome, reseeding of latent reservoirs, recurrence of initial adverse events, decline in CD4+ counts, poor compliance, emergence of virus drug-resistance during interruption). Therefore, and despite the potential interest in this strategy, the use of STIs should currently be restricted to clinical research.

Presenting author: Patrick Yeni

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1 Hopital Bichat-Claude Bernard, Paris, France.

2002-11-17
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