LAUSR

OBJECTIVES Women likely require higher adherence than men to pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) for similar efficacy. Pharmacologic metrics of adherence predict efficacy better than self-report, but expected drug levels (adherence benchmarks) must be established using directly-observed therapy. We sought to evaluate whether tenofovir hair concentrations differ between women and men receiving directly-observed TDF/FTC. METHODS We assessed tenofovir hair concentrations in HIV-uninfected volunteers randomized to receive 100%, 67%, or 33% of daily dosing of TDF/FTC for 12 weeks (DOT-DBS, NCT02022657). Hair samples were collected at dosing weeks 4, 8, and 12 and weeks 3 and 6 during a 12-week washout. Tenofovir concentrations in the proximal 1.5 centimeters of hair (representing ∼6 weeks of exposure) were analyzed using liquid chromatography/tandem mass spectrometry. Linear regression was used to model tenofovir hair concentrations in terms of sex, doses over the prior 6 weeks, and number of days since last dose. RESULTS A total of 264 hair samples were analyzed from 23 female and 24 male participants. Female participants had similar tenofovir hair concentrations to males (estimated fold-difference 0.92, 95% CI 0.75-1.13, p = 0.43). The estimated fold-difference in tenofovir levels for female versus male participants did not appreciably change when age (0.93, CI 0.76-1.15), weight (0.89, CI 0.71-1.11), or race/ethnicity (0.95, CI 0.77-1.17) were added to the model. CONCLUSIONS Women and men have similar adherence benchmarks for tenofovir in hair samples. As pharmacokinetic metrics are increasingly used for PrEP monitoring, these findings provide guidance for assessing adherence via hair concentrations.