7. Project Summary/Abstract The Wits HIV Research Group Clinical Trials Unit (WHRG CTU) under the joint PI Leadership of Ian Sanne and Helen Rees, includes four experienced pleuripotent Clinical Research Sites (CRSs), namely the Wits Helen Joseph Hospital CRS (Dr Sharlaa Badal-Faesen), The Wits RHI Shandukani Maternal and Child CRS (Dr Lee Fairlie), Wits RHI Hillbrow Health Precinct Ward 21 CRS (Prof. Sinead Delaney-Moretlwe) and the Wits RHI Research Centre (Dr Thesla Palanee-Phillips). These four CRSs have capacity to conduct clinical trials across all four NIH Networks, the ACTG, IMPAACT, HPTN and VTN. The CTU’s research agenda includes HIV treatment, HIV-associated infections and HIV-related cancers; HIV prevention; TB treatment and prevention (including MDR-TB) and Hepatitis. The CTU conducts research across all key populations, including adolescent girls and young women, men who have sex with men, transgender populations and female sex workers; as well as vulnerable populations such as neonates, infants, older children, pregnant and breastfeeding women. The CTU has capacity to conduct Investigational New Drug (IND) level trials including phase I/II/II trials, blinded and unblinded randomized trials, across a wide range of products including oral products for treatment and prevention; vaccines for infants, children, adolescents, pregnant women and adults; injectable long acting antiretrovirals for treatment and prevention; monoclonal antibody infusions and microbicides. The expertise, facilities and specialized equipment at each CRS results in the sites conducting these studies at a high level of quality and efficiency. The CTU has in-house laboratory capacity and contracts external laboratories to perform testing to the required Network standards. The four sites are situated in Johannesburg, South Africa’s bustling urban centre and populations included in the CTU research are recruited within Johannesburg, using a targeted approach appropriate for each, and ensuring that hard-to-engage people who may be at highest risk are not excluded. This requires facility- and community-based recruitment and the CTU has a formalized approach, for community engagement across all relevant populations based on good participatory practice principles. The CTU has substantial experience and expertise within all components including but Pharmacy, Regulatory Processes, Data Management, Quality Management, Training and Mentoring and although the four CRSs are distinct, the CTU optimizes efficiencies and collaboration across all CRSs. Experience related to specific populations is shared within the CTU, but also externally locally in South Africa, Regionally and Internationally. The CTU has had over 10 successful IND audits and inspections FDA, EMEA and SAHPRA; and numerous successful PPD and sponsor inspections.

8. Project Narrative The Wits HIV Research Group Clinical Trials Unit (WHRG CTU) consists of four pleuripotent Clinical Research Sites-The Wits Helen Joseph Hospital CRS, The Wits RHI Shandukani Maternal and Child CRS, Wits RHI Hillbrow Health Precinct Ward 21 CRS and the Wits RHI Research Centre. The WHRG CTU research agenda includes HIV treatment, HIV-associated infections and HIV-related cancers; HIV prevention; TB treatment and prevention (including MDR-TB) and Hepatitis. The CTU conducts research across key populations, including adolescent girls and young women, men who have sex with men, transgender populations and female sex workers; as well as vulnerable populations such as neonates, infants, older children, pregnant and breastfeeding women to a high standard of quality, which has been recognized locally and internationally.