The early years of the combination antiretroviral therapy (ART) era have brought about dramatic reductions in the morbidity and mortality associated with HIV infection in industrialized countries and recently, international and local initiatives have allowed access to HAART in the developing world. Preliminary data from my prior work and others have shown that good adherence is feasible in resource-limited settings, but it is unclear whether these results are reproducible in scaled ART programs and what interventions would likely be effective at maximizing adherence in such settings. Peer advocates have been used to improve adherence with medical therapies in a variety of settings. In order to investigate the potential utility of peer advocates in South Africa, I propose to conduct a randomized trial in which 300 patients will be assigned to either peer-DOT-HAART or self-administration of a twice daily combination of Stavudine, Lamivudine and Efavirenz for 24 months. The specific aims of this study are: 1) to evaluate the impact of peer-DOT HAART on control of viral burden and immune restoration as measured by viral load and CD4 T cell counts; 2) to evaluate the impact of DOT-HAART on treatment adherence; 3) the determination of the proportion of genotypic HAART resistance in the peer-DOT vs. self-administered HAART arms; 4) to compare the incidence of new or recurrent opportunistic infection in the peer-DOT vs. self-administered HAART. My hypothesis is that the patients in the peer-DOT-HAART arm will have high levels of treatment adherence and hence more effective in controlling viral burden, thereby limiting the likelihood of virologic failure, drug resistance, and disease progression. This study will generate critical data on an alternative community-based approach of delivering HAART which may become a standard of care throughout sub-Saharan Africa and the developing world. My career development plan is based on a post-graduate training program, which includes comprehensive coursework at the Johns Hopkins University and University of Cape Town, structured mentoring, and guidance from a thesis committee. My career plan and research proposal are consistent with my long-term goals of becoming an effective independent investigator, and optimizing treatment outcomes in HIV-infected in sub-Saharan Africa. [unreadable] [unreadable] [unreadable] [unreadable]