Implementation of highly active antiretroviral therapy (HAART) has led to a substantial decrease in HIV related mortality and morbidity. With this important advance, however, has come a monitoring and decision making process whose complexity challenges the medical care system, particularly in regions where there are large numbers of HIV-infected patients and relatively limited financial and health care resources. Current guidelines emphasize maximal and durable viral load (VL) suppression. However, while successful therapy is demonstrated by restoration of immunity, treatment failure is usually defined as the inability to maintain undetectable viral load, without regard to immune function. This situation often leads to a rapid sequence of therapeutic switches, thus narrowing therapeutic options over time. A monitoring strategy driven primarily by the patient's immune restoration would most likely be as effective in preventing disease progression, would lead to fewer changes in HAART regimens and would be considerably simpler and cost effective. The primary objective is to compare the clinical outcomes of the standard antiretroviral monitoring strategy based on VL (VL-S), with a simpler strategy based on CD4+ cell count (CD4-S). An important secondary objective is to compare the ability of these two strategies to preserve treatment options. The proposed study is a multi-center, Phase III, randomized, non-inferiority trial comparing VL-S with CD4-S among antiretroviral naive immunocompromised adults treated with a PI-containing regimen in Thailand. The study will take place at 30 study sites and the study population will be 700 HIV infected women or men. Index cases will be women screened within the mother-child prevention program, and/or their partners with a CD4+ T cell count between 100 and 250/mm3. For women, randomization will take place after delivery. The initial HAART regimen will be ZDV+3TC+indinavir/ritonavir. Under VL-S, switching is considered when VL rises above 2,000 copies/ml; Under CD4-S, switching is considered when a relative decline in the CD4+ cell count more than 30% from peak values is observed. The primary endpoint for monitoring strategy comparison is clinical failure, defined as confirmed CD4 count below 50/mm 3, first or new AIDS-defining event, or death. A secondary endpoint is the number of drugs exhausted, taking into account cross-resistance mutations and shared toxicities. A pilot pharmacokinetic sub study will evaluate drug levels in the study population.
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