Abstract The University of North Carolina (UNC) Global HIV Prevention and Treatment Clinical Trials Unit (CTU) has a well-established record of high quality, innovative clinical research, strong network and scientific leadership. The CTU engages with critically important populations infected with and at high risk of HIV in southeastern US, southern Africa and southeast Asia. Our CTU is led by three experienced principal investigators (Joseph Eron MD, Mina Hosseinipour MD and David Wohl MD) and will support all four NIH Clinical Trials Networks (CTN); Adult Therapeutic Strategies, HIV Prevention, Vaccine Prevention and Pediatric, Adolescent and Maternal Therapeutic Strategies. Our four experienced Clinical Research Sites (CRS) include Chapel Hill CRS (Adult Strategies, Prevention and Vaccine CTN) led by Dr. Wohl, Greensboro CRS (Adult Strategies, Prevention and Vaccine CTN) led by Cornelius Van Dam MD, Malawi CRS (all four CTN) led by Lameck Chinula MD and Vietnam CRS (Adult Strategies, Prevention and Vaccine CTN) led by Vivian Go PhD. Participants with HIV include those newly diagnosed (including with acute infection), PWH stably suppressed on therapy and PWH with adherence challenges to care or medication and those with drug-resistant HIV. At-risk populations include men who have sex with men (MSM) including young men of color, transgender women (TGW), people who inject drugs (PWID) and African adolescent girls and women including those who are pregnant. We will enroll PWH at risk for comorbidities and PWH or without HIV with co-epidemic pathogens such as tuberculosis (TB) and Hepatitis B virus (HBV). We have skilled, experienced clinical and translational investigators working hand-in-hand with junior investigators with diversity of gender and race, in US and international settings, who will engage and execute the network scientific agenda. A globally representative set of senior scientists and public health leaders on our Scientific and Strategic Advisory Group advise the CTU leadership team. The CTU administration has a highly organized structure that is responsive to our research teams and CRSs. Each CRS engages the communities representing the affected populations in an interactive, open-minded way. State-of-art communication and experienced, outstanding and well-organized laboratory, pharmacy, regulatory, quality and data management support the CTU, CRSs. Using this robust framework the UNC Global CTU is positioned optimally to continue our scientific, and network leadership and clinical trials support to the agenda of all four NIH HIV networks.