Five million people are infected with HIV in South Africa, and the vast majority lack access to antiretroviral therapies (ART) that have made AIDS a manageable disease in the west. Finding efficient ways to deliver ART is therefore a critically important public health issue. This application builds on existing collaborations between the candidate and his proposed mentors, Dr. Kenneth Mayer at Brown University and Dr. Salim Abdool Karim at the University of Natal in Durban, South Africa. For six years, Dr. Lurie worked closely with Dr. Karim at the South African Medical Research Council, where he was the Principal Investigator on a cohort study examining the effect of migrant labor on the spread of HIV. Having completed a Post-Doctoral Fellowship at Brown, Dr. Lurie is now an Assistant Professor of Medicine and Community Health (Research) at Brown University/Miriam Hospital, where he works closely Dr. Mayer. Drawing on the rich academic and research environments of both Brown/Miriam and the University of Natal, the candidate has designed focused training and mentored research activities that will enable him to become an independent investigator in the prevention and treatment of HIV. The main aim of this research is to examine the effect of ART on sexual behavior and treatment adherence in South Africa, two key issues underlying ART's success. Working within an existing NIH-funded randomized controlled trial of people co-infected with TB and HIV in South Africa, the candidate will design culturally specific instruments for behavioral and biological measures of treatment adherence and sexual risk behavior, and will assess whether being on antiretroviral therapy has an impact on risky sexual behavior. The impact of introducing ART has largely focused on individual benefits in terms of decreased morbidity and mortality. But as important is the role of ART in preventing secondary transmission. Since ART lowers the HIV viral load, people on treatment are less infectious and this may result in a decrease in secondary transmission. On the other hand, people on ART live longer, so they potentially have more opportunity to transmit the virus to others. Using the observed data Dr. Lurie will collect, the candidate will work closely with Dr. Geoff Garnett of the Imperial College in London to undertake specific training and to develop mathematical models to quantify the net effect of ART on reducing community HIV incidence.