PROJECT SUMMARY South Africa has the world’s largest antiretroviral therapy treatment program and the second highest TB incidence, with TB the leading cause of death from an infectious agent. South Africa is amongst the top 10 countries with high burden of HIV, TB and drug-resistant TB. The Stellenbosch University Clinical Trials Unit (SUN-CTU) in Cape Town, South Africa is an established, pluripotent, high-capacity research partnership between three Clinical Research Sites (CRSs): the Family Centre for Research with Ubuntu (FAMCRU), the Desmond Tutu TB Centre (DTTC) and TASK Foundation NPC (TASK), ideally aligned for participation in IMPAACT, ACTG, HPTN and expansion to HVTN network studies. The overall SUN-CTU objective is to collaboratively design and implement high-impact clinical research that will result in safe, patient- and-family-centered, effective prevention, treatment and remission of HIV and its related comorbidities, and TB prevention, diagnosis, and treatment, across all age groups. The SUN-CTU aims to address HIV therapeutic research priorities across all ages: FAMCRU will prioritize pharmacokinetics and safety of new antiretrovirals and other interventions across all ages, to minimize long - term treatment complications, antiretroviral resistance, TB/HIV drug-drug interactions, and promote treatment adherence. We will focus on early treated children and adolescents for HIV remission and neurodevelopment and adult Hepatitis, CMV co-infection and non-communicable diseases, HIV-related neurocognitive impairment, mental health and HIV persistence. Second, we will address HIV prevention research priorities in high-risk populations across all ages: Through HPTN, the DTTC will design and implement HIV prevention studies and evaluate long-acting antiretrovirals, multipurpose prevention technologies, broadly neutralizing antibodies (bnAbs), and pre-exposure prophylaxis in adolescents and adults populations. FAMCRU will implement HIV prevention studies in infants, HIV-exposed uninfected children and adolescents, with the full range of interventions including prevention of mother to child transmission, bnAbs and HIV vaccines, through IMPAACT. TASK will conduct HIV vaccine trials. Finally, we will address TB prevention, diagnosis and treatment with/without HIV, across all ages: the SUN-CTU is ideally positioned to evaluate novel and repurposed TB regimens for treatment and prevention across the disease spectrum in adults, with and without drug resistance and HIV. New TB focus areas include adult TB vaccines, extrapulmonary TB, post-TB lung disease, and PK studies in special populations including hospitalized critically ill patients e.g. TB meningitis. DTTC will lead protocols to evaluate novel and repurposed drug regimens to treat and prevent drug-susceptible and drug- resistant TB in infants, children, adolescents, pregnant and breastfeeding women with TB without HIV including specialized site of disease PK studies.

PROJECT NARRATIVE South Africa has the world’s largest HIV treatment program and the second highest TB incidence, with TB the leading cause of death. The overall Stellenbosch Clinical Trials Unit objective is to collaboratively design and implement high-impact clinical research that will result in safe, patient- and-family-centered, effective prevention, treatment and remission of HIV and related comorbidities, and TB prevention, diagnosis, and treatment, across all age groups.