Effect of a Peer Support Intervention for Oral Pre-Exposure Prophylaxis Uptake and Adherence Among Adolescent Girls and Young Women at Risk of HIV Acquisition in Kampala, Uganda: A Randomized Controlled Trial.

INTRODUCTION: Daily oral pre-exposure prophylaxis (PrEP) use remains low among adolescent girls and young women (AGYW). We evaluated whether a peer support intervention improved daily oral PrEP uptake and adherence among AGYW at high risk of HIV acquisition in Kampala, Uganda. METHODS: We conducted an open-label randomized controlled trial (January 2023-June 2024) among 14- to 24-year-olds engaged in sex work. Eligible participants were randomized 1:1 to receive either health worker counselling only (control) or supplemented with peer support (intervention). Peer leaders delivered co-created peer education sessions starting 1 month after enrolment. Participants were followed for 12 months. Co-primary outcomes were PrEP uptake (yes/no) and adherence, evaluated using two separate measures; optimal if: ≥85% pill-counts (primary measure); positive point-of-care urine tenofovir test. Both arms received adherence counselling based on urine results. SECONDARY OUTCOMES: PrEP persistence (time to discontinuation) and cost-effectiveness (cost per disability adjusted life year/DALY averted). Analysis used logistic regression (uptake); generalized estimating equations (adherence), Cox regression (persistence) and incremental cost-effectiveness ratio (ICER) below US$537 per DALY averted was considered cost-effective. RESULTS: We enrolled 394 participants (197 per arm) with a mean age of 19.4 (SD ±2.3) years. The intervention did not impact PrEP uptake (OR 1.15; 95% CI 0.77-1.71) but improved adherence, pill count (OR 2.20; 95% CI 1.23-3.95) and urine assay (OR 2.18; 95% CI 1.22-3.91). Optimal adherence was low but significantly higher in the intervention by both measures: pill count (intervention = 54.8%, control = 39.6%, p = 0.008), urine assay (intervention = 54.8%, control = 40.8%, p = 0.001). Median duration before PrEP discontinuation was 38 days (IQR 0-319 days); intervention (56 days), control (29 days). The intervention had no effect on persistence (HR 0.86; 95% CI 0.64-1.14). It was cost-effective with the urine tenofovir assay (ICER = $459) but not with pill counts (ICER = $581). CONCLUSIONS: This peer-led intervention improved PrEP adherence among AGYW in Kampala and is recommended in high-incidence settings. Urine tenofovir testing can be used to assess adherence if affordable. Enhanced peer support strategies are needed until long-acting PrEP becomes accessible and acceptable. Future research should optimize timing, intensity and delivery models of peer support interventions and integrate them with long-acting PrEP to improve sustainability.