Using Tenofovir Diphosphate Levels to Evaluate Factors Associated With PrEP Non-Adherence and Performance of Indirect Adherence Measures in Latin America: A Prospective, Single-Arm, Open-Label, Multicentre Implementation Study (ImPrEP)

Introduction: Tenofovir-based oral pre-exposure prophylaxis (PrEP) is pivotal for HIV prevention in Latin America. Monitoring PrEP adherence is crucial for maximizing its impact and identifying individuals who may benefit from additional support. We evaluated the performance of indirect adherence measures and factors associated with PrEP non-adherence in Brazil, Mexico and Peru. Methods: ImPrEP was a prospective, multicentre, PrEP implementation study which enrolled 9509 persons from 6 February 2018 to 30 June 2021. For this analysis, we included men who have sex with men (MSM) aged 18–24 years and transgender women aged 18+ years with at least one dried blood spot (DBS) sample collected. Adherence was assessed objectively (tenofovir diphosphate [TFV-DP] levels in DBS) and indirectly (medication possession rate [MPR] and self-report). We estimated area under the curve (AUC) to evaluate the performance of each indirect adherence measure, and the optimal cut-off points for discriminating protective TFV-DP levels based on the Youden index. We used generalized estimating equations to identify factors associated with PrEP non-adherence (TFV-DP<900 fmol/punch). Results: We included 2096 participants (1692 young MSM and 404 transgender women) with 4257 DBS samples. Overall, 62.3% DBS samples showed protective TFV-DP levels, which declined over time (68.8% at week 4 to 33.8% at week 124). Both MPR and self-report demonstrated moderate concordance (AUC: 0.74) with no difference between them (p = 0.79). Optimal cut-offs were 97.6% for MPR and 93.3% for self-report; self-report showed higher sensitivity (84.6%), while MPR had higher specificity (62.9%). Among young adults, PrEP non-adherence was higher among transgender women, participants with lower education and from Peru. Among transgender women, PrEP non-adherence was higher among those with younger age, lower education, and from Peru and Mexico. Self-reported sexual behaviours conveying elevated HIV exposure were associated with lower PrEP non-adherence. Conclusions: MPR and self-report are pragmatic and clinically useful adherence monitoring tools for PrEP programmes in Latin America. Social determinants of health, particularly education, emerged as major drivers of PrEP non-adherence among transgender women and young MSM. To maximize impact, PrEP programmes must prioritize person-centred interventions that address stigma within health services, remove barriers to sustained engagement, strengthen health literacy and include long-acting PrEP modalities.