Project Summary The Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF) and the Walter Reed Army Institute of Research (WRAIR) propose to extend and diversify the existing U.S. Military HIV Research Program (MHRP) Clinical Trials Unit (CTU). The proposed MHRP CTU will leverage its existing network structure, which has been developed with the support of the United States Army, the Division of AIDS (DAIDS) and others, to extend the current DAIDS- funded CTU activity. The current CTU configuration supports the AIDS Clinical Trials Group at two sites and the HIV/AIDS Vaccine Trial Network (HVTN) at two other sites. In this new proposal, we seek to expand to a total of 8 sites all of which will support both the HVTN and the HIV/AIDS Prevention Trials Network (HPTN) and increase ACTG affiliations from 2 to 4 of these sites. To provide stronger support to the new network goals of TB treatment and prevention, MHRP has formed a strategic partnership with the IAVI to form a potent collaboration supporting both the science and development of novel interventions for both HIV and TB prevention and treatment. The MHRP CTU will comprise a core management group located at WRAIR in Maryland, United States and eight international Clinical Research Sites (CRS) located in Africa and Asia. These sites will implement clinical protocols from phase I safety trials to phase III efficacy trials and are located in areas with substantial HIV burden and populations suitable to participate in planned prevention and therapeutic clinical trials. MHRP’s experience and innovation in HIV vaccine research and demonstrated capability to address emerging priorities of HIV cure research will contribute scientifically to the DAIDS vaccine and therapeutics leadership networks. IAVI will contribute both HIV prevention and TB vaccine scientific leadership. The expanded MHRP CTU will bring DAIDS, and the networks MHRP is proposing affiliation with, valuable clinical research capacity with Department of Defense and IAVI supported staff. Specific aims of the proposal include: 1. Provide scientific leadership, novel products and innovative approaches. 2. Provide clinical trial execution of the HIV Vaccine Clinical Trials Network and the HIV Prevention Clinical Trials Network scientific agenda. 3. Provide clinical trial execution of the HIV/AIDS Adult Therapeutics Clinical Trials Network scientific agenda.

Project Narrative Reducing the toll of AIDS and other infectious diseases has been a goal of U.S. National Security Strategy since 2002. TB is a leading cause of mortality globally, particularly in HIV infected populations. Despite progress in blunting the epidemics through broad access to treatment and PrEP, eradication will require clinical research leading to an effective HIV vaccine and treatments that cure or limit disease progression.