Project summary The San Francisco Bay Area has experienced a particularly intense HIV epidemic, with men who have sex with men (MSM), Black, and Latinx populations most heavily impacted in the region; and transpeople and people who inject drugs important populations for engagement. Drs. Susan Buchbinder and Diane Havlir are scientific leaders in HIV prevention and treatment, respectively. Together they will lead the San Francisco Bay Area Clinical Trials Unit (SFBay CTU), affiliated with the ACTG, HPTN, and HVTN. This integrated research organization will accomplish 3 specific aims through these Networks: 1) advance prevention and treatment science and their intersection within the Clinical Trials Networks; 2) implement clinical trials efficiently and with excellent adherence to protocol while engaging diverse communities; and 3) develop a new generation of diverse leaders in HIV prevention and treatment science. Drs. Buchbinder and Havlir are joined by a diverse pool of talented investigators who have provided leadership across the Networks, serving on numerous scientific leadership committees and working groups and chairing a range of prevention and treatment protocols. The two Clinical Research Sites, the Bridge HIV CRS (affiliated with HVTN and HPTN and led by Dr. Hyman Scott) and the UCSF CRS (affiliated with ACTG and led by Dr. Annie Leutkemeyer) have records of excellence in enrollment, retention, and adherence to protocol requirements, and actively engage local communities throughout the San Francisco Bay Area. This application represents a renewal of the SFBay CTU, with several improvements, including new leadership by an accomplished, diverse group of investigators; integration of community programs into a single, status-neutral team; expansion of community engagement and recruitment into the East and South Bays of San Francisco; and full integration of early stage investigators in all aspects of the science of the SFBay CTU. Through a smoothly running research infrastructure, divided into Scientific, Operational, and Community Engagement Steering Committees, the SFBay CTU is committed to continued leadership in the ACTG, HPTN, and HVTN, and contributing to breakthroughs in the science of HIV prevention, treatment, and cure.