190 When to Interrupt Antiretroviral Therapy? H Guenthard Univ Hosp Zurich, Switzerland

Background: Over recent years, interrupting potent antiretroviral combination therapy has rapidly evolved to become a major field of HIV research. This is a surprising development if one considers that introduction of combination antiretroviral therapy by far has been the most successful therapeutic intervention since the beginning of the AIDS epidemic.
Methods: Reasons allowing for conducting clinical studies of treatment interruptions were based on the accumulating evidence that eradication of HIV-1 is very unlikely to be achieved with current antiretroviral regimens, even if treatment is maintained for decades. Moreover, the increasing prevalence of serious side effects, toxicities, metabolic disorders, the emergence of drug resistance in a considerable fraction of patients (pts) undergoing antiretroviral treatment, high costs and the limited availability of antiviral drugs in resource poor countries has forced and stimulated physicians and pts to search for new therapeutic strategies.
Results: Treatment guidelines have been changed in favor of delaying initiation of treatment in chronically infected patients as long as possible to minimize negative drug effects but to start on time to hinder the occurrence of opportunistic infections. Furthermore, treatment interruptions have been studied in pts who initiated treatment during acute and chronic HIV infection. These trials have mainly addressed three questions: Firstly, whether protective immune responses may be induced, secondly, whether drug exposure can be limited in order to minimize toxicity and reduce costs and thirdly, whether response to salvage regimens in pts with multiple treatment failures can be improved. Whenever, treatment interruptions are conducted one has to weigh possible benefits against potential risks of this strategy, such as CD4 cell decline, selection of HIV-1 drug resistance, increasing risk of HIV-transmission, emergence of acute retroviral syndrome, reseeding of viral reservoirs and potential decrease of adherence to subsequent therapy.
Conclusions: In summary, at present, treatment interruption remains an investigational treatment strategy, because too many issues have not finally been resolved yet. Whether treatment interruption will have an established role in antiretroviral treatment remains to be determined in long-term randomized clinical trials.