ACTG A5175: ONCE-DAILY ARV THERAPY FOR HIV-1 IN RESOURCE-LIMITED SETTINGS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Most previous trials of antiretroviral therapy (ARV) have been conducted in economically developed countries of North America and Europe. Most HIV-1-infected persons live in resource-limited areas of the world. Existing data suggest that strict adherence to treatment is a major determinant of ARV efficacy. Since factors that could affect adherence (e.g., drug toxicity, co-morbidities, and nutritional status) are likely to differ in resource-limited countries, the relative efficacy of ARV regimens in such settings may also differ. One approach to increase adherence is to decrease the complexity of ARV regimens by decreasing the number of pills in the regimen and the number of doses per day. It is expected that simple once-daily regimens will increase adherence and therefore ARV efficacy. The availability of once-daily regimens will also facilitate the implementation of directly observed models of ARV delivery. Thus, three-drug ARV combinations that require fewer pills dosed once-daily have potential advantages for the treatment of HIV-1 infection in resource-limited settings. This study, therefore, hypothesizes that once-daily treatment with 2 nucleoside analogue reverse transcriptase inhibitors (NRTIs) plus a protease inhibitor (PI) or plus a non-NRTI (NNRTI) is not inferior to a twice-daily regimen containing the NNRTI in a resource-limited setting. Endpoints of the study are 1) death, 2) disease progression after 12 weeks of therapy, or 3) virologic failure defined as an HIV RNA>1,000 copies/ml on 2 successive measurements after 16 weeks of treatment. In Step 1 (10 patients per site), about 1500 treatment-na¿ve patients (including previously pregnant women who have been treated with short-course ZDV and/or NVP for HIV prophylaxis of mother-to-child transmission) in the United States and at International ACTG sites will be randomized into 3 arms: 1) 3TC/ZDV BID + EFV OD; 2) FTC/ATV/DDI-EC OD; 3) FTC/TDF/EFV OD. In Step 2, patients who qualify for a switch - e.g., virologic failure, disease progression, decreased CD4 count <50% maximum - will be offered a switch to any viable combination of three or more of the A5175-provided study drugs used in Step 1 and/or non-study drugs not available through A5175, at the discretion of the site investigator. Enrollment will be stratified by country of origin and by HIV RNA (either > or < 100,000 copies per ml). Intent-to-treat analysis performed when 30% of