Unraveling PrEP persistence: mental health and substance use among adolescent girls and young women in a PrEP implementation program

Objective: To examine associations between mental health, substance use, and PrEP persistence among South African adolescent girls and young women (AGYW). Design: Longitudinal analysis of a decentralized PrEP implementation program. Methods: We analyzed data from FastPrEP, a youth-focused program delivering PrEP with peer-navigator support through community-based mobile clinics and public clinics near Cape Town. Female participants aged 15–29 years who received a one-month supply of daily oral PrEP at program enrollment were included. Moderate to severe depression/anxiety symptoms (PHQ-4 ≥6) and hazardous alcohol use (AUDIT-C ≥3) were assessed at enrollment. Log-binomial regression was used to estimate overall and age-stratified adjusted prevalence ratios (aPRs) for associations with PrEP persistence at the one-month follow-up visit. Results: From April 2022 to April 2024, 6,271 AGYW were enrolled in FastPrEP and dispensed daily oral PrEP (median age 21 years); 75% enrolled at mobile clinics. At enrollment, 8% reported moderate to severe depression/anxiety symptoms and 50% hazardous drinking. Only 10% returned and received PrEP within a 28-day window of their one-month follow-up visit. Moderate-severe depression/anxiety symptoms were associated with greater PrEP persistence (aPR=1.37, 95% CI 1.04, 1.79), as was hazardous drinking (aPR=1.46, 95% CI 1.23, 1.75). Associations were strongest among AGYW aged 15–19 years (depression/anxiety: aPR=1.71, 95% CI 1.11, 2.65; hazardous drinking: aPR=1.60, 95% CI 1.16, 2.19). Conclusions: Contrary to expectations, mental health and substance use challenges were associated with greater short-term PrEP persistence, particularly among younger AGYW. These findings suggest that youth-centered, peer-supported delivery models may help sustain engagement among higher-risk AGYW.