The effectiveness of oral emtricitabine (FTC)/tenofovir (TFV) disoproxil-fumarate pre-exposure prophylaxis (PrEP) is highly dependent on adherence. Given limitations of self-reported adherence, pharmacologic measures are useful for understanding patterns of adherence and identifying predictors of consistent PrEP use.
We analyzed data from HPTN 067, a trial of intermittent and daily PrEP completed in 2014. We included men who have sex with men (MSM) in Bangkok, Thailand, and Harlem, United States. Participants were randomly assigned to daily, time-driven (one dose twice/week plus one dose after sex), or event-driven (one dose before and after sex) oral PrEP regimens. Study visits occurred at weeks 0, 4, 12, and 24 post-randomization to assess FTC and TFV levels. Plasma and hair samples measured short and long-term drug exposure, respectively. Electronic pill bottle data (Wisepill™) were collected weekly. Potential predictors of adherence were measured at baseline (e.g., demographics, alcohol use) and longitudinally (e.g., sexual behavior). We estimated Pearson correlation coefficients among measures and assessed predictors of log-transformed plasma and hair drug levels using linear mixed models. Pharmacologic measures below the detection limit were set equal to that limit prior to log transformation.
Among the 350 randomized MSM at the two sites, half had completed college (N=179; 51.1%) and the median age was 31 years (IQR: 25–38 years). At baseline, 20.6% reported heavy alcohol use (N=72) and the median number of sex partners in the prior three months was 4 (IQR: 2–8). Across all arms and follow-up periods, FTC and TFV hair concentrations were moderately correlated with plasma concentrations and Wisepill™ data (Pearson coefficients >0.28). In multivariate models, being enrolled at the Harlem site, being in the time- or event-driven arms, and having less than college education were associated with lower hair FTC/TFV levels, while heavy alcohol use was associated with higher hair levels (Table). In models evaluating plasma levels, similar results were seen for site and study arm, but older age and greater number of sex partners were significantly associated with higher plasma drug levels.
In HPTN 067, plasma and hair drug concentrations and Wisepill™ data correlated with one another and served as complementary measures of PrEP adherence. Site, study arm, education, age, alcohol use, and sexual behavior influenced patterns of short and long-term PrEP adherence.