Project Summary/Abstract For over 2 decades the University of Zimbabwe-University of California, San Francisco Clinical Trials Unit (UZ- UCSF CTU) has continuously conducted high quality Phase I-IV clinical trials, utilizing experienced teams of multidisciplinary, cross-trained investigators, and research staff across the multi-Network CTU. The CTU is a center of excellence in the prevention and control of HIV/AIDS and has contributed to the global understanding of HIV epidemiology and pathogenesis, policy, and standards of care. In the current funding cycle, the CTU enrolled over 6,700 participants in 48 clinical trials across all 5 NIH-funded Networks (ACTG, IMPAACT, HPTN, HVTN, MTN) at 7 Clinical Research Sites (CRSs), generating 138 scientific articles and informing Zimbabwe’s health policy. The CTU has innovated to overcome operational challenges occasioned by the political and economic environment in Zimbabwe. The CTU proposes to continue to develop its scientifically rigorous and well-managed CTU to support the scientific agendas of the 4 proposed Networks (ACTG, IMPAACT, HPTN, HVTN), train the next generation of research leaders in Zimbabwe, and contribute to the control and prevention of HIV and TB in Zimbabwe and globally, with 4 Specific Aims: Specific Aim 1. Lead robust contributions to the research agendas of the ACTG, IMPAACT, HPTN, HVTN Networks; a) Continue to advance evaluation of novel and durable systemic ARV-based therapeutic and preventive strategies for: (i) control of HIV replication in the absence of ART; (ii) control of communicable and non-communicable comorbidities; and (iii) prevention of HIV in Key Populations, including adolescent girls and young women, men who have sex with men, and female sex workers by evaluating novel PrEP drug delivery systems; b) Continue evaluation of novel preventative and therapeutic vaccine candidates and broadly neutralizing antibodies for HIV/TB control among children, adolescents, and adults; c) Implement integrated strategies to evaluate socio- behavioral, biomedical, and structural interventions for HIV prevention among high-risk Key Populations while optimizing treatment outcomes among children, adolescents, and adults living with HIV; d) Investigate new product acceptability, uptake, and adherence using mixed methods to assess the effectiveness of novel approaches, including Multi-Purpose Prevention Technologies; Specific Aim 2. Intensify community engagement at all stages of research and evolve Community Advisory Board membership to represent, mobilize, and empower Key Populations, in support of the UNAIDS 95-95-95 targets; Specific Aim 3. Maintain and adapt our CTU’s efficient and sophisticated centralized research infrastructures across the CRSs and the Laboratory, Pharmacy, Community, Regulatory, Quality Management, Administration and Finance Departments to drive compliance and ensure efficient execution of trials; and Specific Aim 4. Fortify the CTU’s role as a local, regional, and global knowledge hub with investments in training and mentorship for the next generation of scientific and community-based leaders.

Project Narrative This award will support the CTU to continue its third decade of high impact, globally relevant HIV and TB prevention and therapeutic research, aligned with Network scientific objectives, and in support of Zimbabwe Ministry of Health policy goals, and designed to advance progress toward UNAIDS 95-95-95 targets. The CTU will help to develop future research aims and disseminate lessons learned to inform local, regional, and international efforts and best practices aimed at changing the trajectory of the HIV pandemic, and ultimately, result in its control.