The HIV pandemic is one of the greatest ongoing threats to health and development, over 30 years past its recognition. The NIAID-funded Clinical Trials Networks have played critical roles in the coordinated response to key research questions in the HIV/AIDS field. The proposed Vanderbilt Clinical Trials Unit (CTU) is a partnership between Vanderbilt University and Washington University, comprising three top-performing incumbent Clinical Research Sites (CRSs) that span the therapeutics mission of the AIDS Clinical Trials Group (ACTG) and the vaccine mission of the HIV Vaccine Trials Network (HVTN). This builds upon the already established partnership between the Vanderbilt Therapeutics CRS and the Vanderbilt Vaccine CRS, and adds a new partnership with the Washington University Therapeutics CRS. The latter two sites have been members of the HVTN and ACTG since the inception of these Networks in 1987-1988. The leaders of this CTU have made high-impact, unique scientific and programmatic contributions to the Networks in areas that include human genomics and neurological aspects of HIV disease. Moving forward this CTU will continue its track record of programmatic impact by leveraging Vanderbilt's institutional strength in biomedical informatics to implement flexible, real-time, shareable informatics tools to optimize CTU performance. This CTU also benefits from close ties to other major NIH programs including Vanderbilt's roles as Coordinating Center for the nationwide network of approximately 60 Clinical and Translational Science Awards (CTSA), for the seven worldwide regions of the NIAID-sponsored International Epidemiologic Databases to Evaluate AIDS (leDEA), and for the seven countries of leDEA's Latin American region. During the proposed finding period the Vanderbilt CTU will make substantial contributions to the ACTG's scientific priorities focused on HIV/AIDS, tuberculosis, and viral hepatitis, and will make substantial contributions to the HVTN's major scientific priority of developing and testing a safe and effective vaccine for HIV.