The efficacy of pre-exposure-prophylaxis (PrEP) in HIV can diminish with poor adherence; pharmacologic measures of drug exposure have proven critical to PrEP trial interpretation. We assessed drug exposure in hair against other pharmacologic and more routinely-used measures to assess pill-taking.
DESIGN: Participants were randomized to placebo, daily PrEP or intermittent PrEP in order to evaluate safety and tolerability of daily-versus-intermittent tenofovir/emtricitabine (TFV/FTC) in two phase-II PrEP clinical trials conducted in Africa. Different measures of drug exposure, including self-report, medication-electronic-monitoring-system (MEMS)-cap openings, and TFV/FTC levels in hair and other biomatrices, were compared.
METHODS: At weeks 8 and 16, self-reported pill-taking, MEMS-cap openings, and TFV/FTC levels in hair, plasma, and peripheral-blood-mononuclear-cells (PBMCs) were measured. Regression models evaluated predictors of TFV/FTC concentrations in the three biomatrices; correlation coefficients between pharmacologic and non-pharmacologic measures were calculated. Both trials were registered on ClinicalTrials.gov (NCT00931346/NCT00971230).
RESULTS: Hair collection was highly feasible and acceptable (100% week 8; 96% week 16). In multivariate analysis, strong associations were seen between pharmacologic measures and MEMS-caps openings (all p<0.001); self-report was only weakly associated with pharmacologic measures. TFV/FTC hair concentrations were significantly correlated with levels in plasma and PBMCs (correlation coefficients 0.41-0.86, all p<0.001).
CONCLUSIONS: Measuring TFV/FTC exposure in small hair samples in African PrEP trials was feasible and acceptable. Hair levels correlated strongly with PBMC, plasma concentrations, and MEMS-caps openings. As in other PrEP trials, self-report was the weakest measure of exposure. Further study of hair TFV/FTC levels in PrEP trials and demonstration projects to assess adherence/exposure is warranted.