The Seattle-Lausanne Clinical Trials Unit (CTU) has a common vision to live in a world without new HIV infections and free of AIDS-related morbidity and death. To this end, we are committed to accelerate progress over the next seven years to: 1) develop a globally effective HIV vaccine, a combination broad neutralizing antibody immunoprophylaxis regimen that can prevent HIV, and an improved vaccine regimen to prevent Mycobacterium tuberculosis infection; and 2) discover novel and improved therapies that can effectively treat all persons living with HIV, prevent HIV disease and its co-morbidities, and lead to sustained viral remission without the need for ongoing treatment. In this renewal application for NIAID funding in 2020-2027, our CTU proposes continued support of the scientific priorities of the HIV Vaccine Trials Network (HVTN) and the HIV Adult Therapeutic Network (ACTG), through our three existing and highly integrated Clinical Research Sites (CRSs): the Seattle Vaccine Trials Unit (HVTN site), the Lausanne Vaccine and Immunotherapy Center (HVTN site) and the University of Washington AIDS Clinical Trials Unit (ACTG site). Our CTU is operating in a productive and intense period of clinical research on behalf of the networks, and we anticipate a seamless transition from our current portfolio to the proposed new studies initiated in the next cycle. Our CTU leaders and co-investigators are valuable members of the networks’ leadership and scientific committees; they chair and participate in high profile first-in-human studies and bring innovative designs to gain insights into the mechanisms by which candidate vaccines and novel therapeutics achieve their desired responses. Furthermore, our CRSs will continue to enroll and follow target populations in clinical trials and contribute outstanding data to advance promising immune-based, antiviral, and other therapeutic strategies. To achieve our vision and address the networks’ priorities, in Aim 1 we will harness the collective, diverse expertise of three internationally recognized thought leaders in the HIV field to provide scientific leadership and innovation to the HVTN and ACTG. In parallel, our CTU will advance the research careers, leadership skills and opportunities for early-stage physician scientists to foster the next generation of network investigators. In Aim 2, our governance and administrative structure will provide a transparent process for decision-making and effective oversight of communication, resource allocation, pharmacy, clinical and regulatory operations, and quality management to enable a highly integrated, productive CTU. In partnership with the HVTN and ACTG, in Aim 3 our three CRSs will conduct phase 1-4 clinical trials with the CTU support necessary to ensure the highest quality standards. In Aim 4, we will continue to involve our community partners to ensure their input and support, and to optimize enrollment and engagement of relevant populations in our clinical rese...