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Methods: We conducted a retrospective programmatic analysis of routinely collected PrEP data from Mbale Regional Referral Hospital between 2019 and 2025. The study population included HIV-negative AYAs aged 15–29 years initiating PrEP. The primary outcome was early PrEP persistence, defined as attendance at ≥2 follow-up visits versus early discontinuation after one visit. Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Models were adjusted for age group, sex at birth, marital status, education level, religion, population category, service delivery point, psychoactive drug use in the past six months, and experience of gender-based violence. Sensitivity analyses restricted the sample to individuals with documented peer outreach contact.
Results: Among 2,892 AYAs initiating PrEP, 36.7% were persistent beyond the first follow-up visit. In adjusted analyses, those who identified as male (aOR 1.41; 95% CI 1.09–1.82; p = 0.008), being married (aOR 1.84; 95% CI 1.51–2.23; p < 0.001), and having a baseline STI syndrome (aOR 2.95; 95% CI 1.60–5.42; p < 0.001) were associated with higher odds of early PrEP persistence. Persistence was lower among Christian participants compared with Muslims (aOR 0.82; 95% CI 0.67–0.99; p = 0.048). In sensitivity analyses excluding individuals without peer outreach contact, associations remained consistent, with additional evidence of higher persistence among sex workers and reduced persistence in community-based service delivery settings.
Conclusions: Early PrEP persistence among AYAs in Eastern Uganda remains suboptimal and is influenced by social, clinical, and service-delivery factors. Integrating STI services, strengthening peer-led outreach, and tailoring delivery models to population-specific needs may improve early PrEP engagement among young people at high risk of HIV.