Comparing pharmacologic measures of tenofovir exposure in a U.S. pre-exposure prophylaxis randomized trial

<div><p>It is critical to assess adherence to pre-exposure prophylaxis (PrEP) in clinical trials. The relationship between pharmacokinetic measures of PrEP adherence and other adherence measures used in PrEP trials requires further characterization. Plasma, peripheral blood mononuclear cells (PBMCs), and hair samples were collected from 88 HIV-uninfected men who have sex with men in a placebo-controlled randomized PrEP trial; announced pill counts, medication electronic monitoring (MEMS), and self-report using visual analog scale (VAS) were also collected. Tenofovir (TFV or TFV-DP) in plasma, hair, and PBMCs were quantified. Proportions with drug detection, Spearman correlation coefficients, and univariate and multivariable regression models were used. Drug detection in plasma, PBMC, and hair samples was highly concordant with treatment arm assignment. TFV or TFV-DP levels were detected in most active-arm participants: 44/47 (94%) in plasma, 46/47 (98%) in hair, and 44/47 (94%) in PBMCs and in only 1/41 placebo arm participant. Correlation coefficients were r = 0.59 for plasma and PBMC, r = 0.34 for PBMC and hair and r = 0.36 for plasma and hair. MEMS and announced pill-counts were moderately correlated (r = 0.52) but less so with pharmacologic measures (range of r = 0.12 to 0.38). Self-reported adherence by visual analog scale demonstrated essentially no correlation with drug levels (r = 0.06 for hair, PBMC or plasma) and was a poor indicator of exposure to study product. Indices of drug exposure are important indicators in assessing adherence to PrEP; accounting for variability between measures may improve interpretation and use of adherence measures in future PrEP studies.</p><p>Clinical trial registration</p><p>Clinical Trials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT00131677" target="_blank">NCT00131677</a></p></div