Pre-exposure Prophylaxis Outcomes from a Multilevel Cluster-Randomized Trial Among Adolescent Girls and Young Women in Tshwane, South Africa.

Pre-exposure prophylaxis (PrEP) effectively reduces HIV incidence among South African adolescent girls and young women (AGYW), but barriers to access and sustained use remain. We evaluated the effects of a clinic-level stigma and discrimination (S&D) training and the Young Women's Health CoOp (YWHC) intervention on oral PrEP outcomes among AGYW aged 16-24 years (N = 802) in Tshwane (Pretoria), South Africa. Using a modified 2 × 2 factorial cluster-randomized trial, 12 clinics and their catchment areas were assigned to one of four study arms based on receipt of S&D training for clinic staff and delivery of the YWHC intervention to AGYW. Outcomes included PrEP readiness (self-report), uptake (medical records), adherence, and persistence (dried blood spots), measured at baseline and 3-, 6-, and 9-month follow-up. Multilevel modeling showed that PrEP readiness scores were higher at follow-up among AGYW in the control arm than among those in intervention arms (p < 0.05). Differences in PrEP uptake were not statistically significant (p = 0.11), although they were clinically meaningful. AGYW attending clinics that received S&D training were more than twice as likely to initiate oral PrEP as participants in the control arm. AGYW who received the YWHC intervention were more likely to adhere to oral PrEP than those in the control arm (p ≤ 0.05). Participants in all intervention arms were also more likely to persist with PrEP use over time than controls (p < 0.05). These findings suggest that clinic- and individual-level interventions can optimize PrEP initiation, adherence, and persistence among AGYW.