PrEP Disengagement and Retention Trajectories Among Adolescents and Young Adults from Key and Priority Populations In Uganda

Background: Adolescents and young adults (AYAs) from key and priority populations face persistent challenges with sustained engagement in HIV pre-exposure prophylaxis (PrEP) care. While PrEP initiation has expanded across sub-Saharan Africa, evidence on long-term retention and drivers of disengagement among AYAs remains limited. We examined time to PrEP disengagement and associated factors among AYAs initiating PrEP in eastern Uganda.

Methods: We conducted a retrospective longitudinal analysis of routinely collected program data for AYAs aged 15–29 years from key and priority populations who initiated PrEP between 2019 and 2025 at Mbale Regional Referral Hospital. Time to PrEP disengagement was assessed using Kaplan–Meier survival analysis and Cox proportional hazards regression. Multivariable models was adjusted for sociodemographic, relational, behavioral, and service delivery factors. We conducted sensitivity analyses that was redefined from the time origin to day 91 following PrEP initiation to reflect the programmatic 90-day grace period.

Results: Among 3,553 AYAs initiating PrEP, the median time to disengagement was 284 days (95% CI: 273–295), and the median age was 24 years (interquartile range [IQR]: 20–26). The probability of remaining engaged in PrEP care declined from 60.1% at 90 days to 20.2% at 365 days. Survival patterns differed significantly by population category and sex at birth, but not by age group. In adjusted analyses (N = 3,391), knowledge of a partner’s HIV status (adjusted hazard ratio [aHR] = 2.04; 95% CI: 1.82–2.29) and initiation through community-based services (aHR = 1.42; 95% CI: 1.17–1.72) were associated with a higher hazard of disengagement. Married participants had lower hazards of disengagement as compared to those who identified as singles (aHR = 0.69; 95% CI: 0.64–0.76). Reporting an STI syndrome (aHR = 0.42; 95% CI: 0.32–0.55) or recent gender-based violence (aHR = 0.76; 95% CI: 0.60–0.96) was associated with reduced disengagement. Findings were consistent in sensitivity analyses.

Conclusions: PrEP disengagement among AYAs occurs rapidly following initiation, with substantial attrition within the first year. Relational factors, service delivery modality and population-specific vulnerabilities strongly shape PrEP retention trajectories. Risk-responsive, differentiated PrEP delivery strategies that integrate STI and GBV services and strengthen retention support are needed to improve sustained engagement among AYAs.