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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
2UM1AI069521-15
Application #
10057458
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Pouliot, Eileen M
Project Start
2007-04-15
Project End
2027-11-30
Budget Start
2020-12-01
Budget End
2021-11-30
Support Year
15
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Stellenbosch University Tygerberg Campus
Department
Type
DUNS #
569118040
City
Cape Town
State
Country
South Africa
Zip Code
8000
Swindells, S; Gupta, A; Kim, S et al. (2018) Resource utilization for multidrug-resistant tuberculosis household contact investigations (A5300/I2003). Int J Tuberc Lung Dis 22:1016-1022
Seddon, J A; Weld, E D; Schaaf, H S et al. (2018) Conducting efficacy trials in children with MDR-TB: what is the rationale and how should they be done? Int J Tuberc Lung Dis 22:24-33
Cranmer, Lisa M; Draper, Heather R; Mandalakas, Anna M et al. (2018) High Incidence of Tuberculosis Infection in HIV-exposed Children Exiting an Isoniazid Preventive Therapy Trial. Pediatr Infect Dis J 37:e254-e256
Byabene, A K; Fortes-Déguénonvo, L; Niang, K et al. (2017) Optimal antiretroviral therapy adherence as evaluated by CASE index score tool is associated with virological suppression in HIV-infected adults in Dakar, Senegal. Trop Med Int Health 22:776-782
Nachega, Jean B; Uthman, Olalekan A; Mofenson, Lynne M et al. (2017) Safety of Tenofovir Disoproxil Fumarate-Based Antiretroviral Therapy Regimens in Pregnancy for HIV-Infected Women and Their Infants: A Systematic Review and Meta-Analysis. J Acquir Immune Defic Syndr 76:1-12
Innes, Steve; van Toorn, Ronald; Otwombe, Kennedy et al. (2017) Late-Onset Hiv Encephalopathy In Children With Long-Standing Virologic Suppression Followed By Slow Spontaneous Recovery Despite no Change In Antiretroviral Therapy: 4 Case Reports. Pediatr Infect Dis J 36:e264-e267
Nachega, Jean B; Skinner, Donald; Jennings, Larissa et al. (2016) Acceptability and feasibility of mHealth and community-based directly observed antiretroviral therapy to prevent mother-to-child HIV transmission in South African pregnant women under Option B+: an exploratory study. Patient Prefer Adherence 10:683-90
Zachor, Hadas; Machekano, Rhoderick; Estrella, Michelle M et al. (2016) Incidence of stage 3 chronic kidney disease and progression on tenofovir-based regimens. AIDS 30:1221-8
Maritz, E R; Montepiedra, G; Liu, L et al. (2016) Source case identification in HIV-exposed infants and tuberculosis diagnosis in an isoniazid prevention study. Int J Tuberc Lung Dis 20:1060-4
Nachega, Jean B; Adetokunboh, Olatunji; Uthman, Olalekan A et al. (2016) Community-Based Interventions to Improve and Sustain Antiretroviral Therapy Adherence, Retention in HIV Care and Clinical Outcomes in Low- and Middle-Income Countries for Achieving the UNAIDS 90-90-90 Targets. Curr HIV/AIDS Rep 13:241-55

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