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Comparing the novel method of assessing PrEP adherence/exposure using hair samples to other pharmacologic and
Sanjiv M Baxi1, Albert Liu, Peter Bacchetti
1*Divisions of HIV/AIDS and Infectious Diseases, Department of Medicine, University of California San Francisco, San Francisco, CA; †Bridge HIV, San Francisco Department of Public Health, San Francisco, CA; ‡Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA; §Kenya AIDS Vaccine Initiative, Nairobi, Kenya; ‖Centre for Geographic Medicine Research Coast, Kenya Medical Research Institute, Kilifi, Kenya; ¶Nuffield Department of Clinical Medicine, University of Oxford, Headington, United Kingdom; #MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda; **Center for Global Health, Massachusetts General Hospital, Boston, MA; ††Gilead Sciences, Foster City, CA; ‡‡Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; §§Department of Pharmaceutical Sciences, University of Colorado, Aurora, CO; ‖‖Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA; and ¶¶International AIDS Vaccine Initiative, New York, NY.
Objective:
The efficacy of pre-exposure prophylaxis (PrEP) in HIV will 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 to evaluate safety and tolerability of daily versus intermittent tenofovir/emtricitabine (TFV/FTC) in 2 phase II PrEP clinical trials conducted in Africa. Different measures of drug exposure, including self-report, medication event monitoring system (MEMS)-caps openings, and TFV/FTC levels in hair and other biomatrices were compared.
Methods:
At weeks 8 and 16, self-reported pill-taking, MEMS-caps 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 3 biomatrices; correlation coefficients between pharmacologic and nonpharmacologic measures were calculated. Both trials were registered on ClinicalTrials.gov (NCT00931346/NCT00971230).
Results:
Hair collection was highly feasible and acceptable (100% in week 8; 96% in 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.
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