The population-level reductions in HIV incidence attributed to pre-exposure prophylaxis (PrEP) have not been fully realized among sexual, gender, and racial/ethnic minority youth. P3 (Prepared, Protected, emPowered) is a comprehensive mobile application (app) intervention developed to support PrEP adherence through gamification, medication tracking, and social engagement. A randomized controlled trial was conducted with 246 young men who have sex with men (YMSM) and young transgender women who have sex with men (YTWMSM) currently on or planning to begin PrEP. Participants were randomized in a 1:1:1 ratio to: standard of care (SOC), P3 app (P3), or P3 app plus in-app adherence coaching (P3+). Adherence was measured at 3- and 6- months post enrollment by emtricitabine-triphosphate (FTC-TP) and tenofovir-diphosphate (TFV-DP) levels in dried blood spots consistent with PrEP use > 4 days/week. The primary outcome was the difference in the proportion adherent comparing P3/P3+ to SOC. P3/P3+ was associated with a higher proportion adherent compared to SOC for both outcome measures. At 3 months, the estimated increase in the proportion adherent was 0.13 (95% CI: 0.00, 0.27, p: 0.05) and 0.12 (95% CI: -0.03, 0.26, p: 0.11) for TFV-DP and FTC-TP, respectively. Estimated adherence was higher, but not statistically different, in P3+ compared to P3, for both TFV-DP and FTC-TP. Receipt of P3 (P3 or P3+) is associated with an increase in PrEP adherence among YMSM and YTWSM at 3 months. Additional analyses to discern the role of app usage and sociodemographic and behavioral factors on intervention effects are warranted.
