This application is submitted on behalf of the ongoing HIV Malawi HIV Research Consortium (HRC) which includes the College of Medicine (COM) in Malawi, the University of North Carolina (UNC) at Chapel Hill, NC and the Johns Hopkins University (JHU) Bloomberg School of Public Health in Baltimore, MD. In recognition of the long history of these collaborations, JHU will continue to serve as the primary grantee institution and lead the Administrative Component of the proposed Clinical Trials Unit (CTU). This country-wide consortium includes the resources of the two main medical facilities in Malawi, the Queen Elizabeth Central Hospital in Blantyre and the Kamuzu Central Hospital in Lilongwe (they will represent the Clinical Research Sites). The HIV/AIDS epidemic is severely impacting the health of children, adolescents, men and women in Malawi. In some of these populations, the HIV prevalence is more than 30% and HIV incidence is more than 4 per 100 person-years. The Malawi HRC has developed a long-term collaboration focused on a wide spectrum of HIV research that includes most aspects of HIV prevention, HIV treatment and care and nascent vaccine efforts. This consortium has inspired several cutting-edge research projects and very extensive training and technology transfers. Each participating institution brings essential resources to this collaboration: the COM in Malawi provides a critical ink to all aspects of the health care infrastructure, appropriate patient populations, and in-country personnel required for a successful research program;Johns Hopkins University has provided leadership, training, clinical and laboratory resources, and a diverse scientific research agenda that led to innovative interventions;and UNC has provided access to new populations, increased capacity for biological research, pioneered research on sexually transmitted infections, and increased focus on issues of HIV treatment. The Aims of this Proposal are I) To implement clinical trials that assess safety, efficacy and acceptability of appropriate interventions in all high priority research areas;II) To expand as needed to additional populations to further investigate HIV pathogenesis, evaluate the development of treatment and prevention strategies that are applicable to populations in resource-constrained settings, and respond to emerging scientific opportunities;and III) To work collaboratively with the Clinical Trials Networks Leadership to contribute to the scientific agenda. ADMINISTRATIVE COMPONENT: