title: Comparing the novel method of assessing PrEP adherence/exposure using hair samples to other pharmacologic and traditional measures.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: *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.
authors.forename: Sanjiv M
authors.initials: SM
authors.lastname: Baxi
authors.forename: Albert
authors.initials: A
authors.lastname: Liu
authors.forename: Peter
authors.initials: P
authors.lastname: Bacchetti
authors.forename: Gaudensia
authors.initials: G
authors.lastname: Mutua
authors.forename: Eduard J
authors.initials: EJ
authors.lastname: Sanders
authors.forename: Freddie M
authors.initials: FM
authors.lastname: Kibengo
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Haberer
authors.forename: James
authors.initials: J
authors.lastname: Rooney
authors.forename: Craig W
authors.initials: CW
authors.lastname: Hendrix
authors.forename: Peter L
authors.initials: PL
authors.lastname: Anderson
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.forename: Frances
authors.initials: F
authors.lastname: Priddy
authors.forename: Monica
authors.initials: M
authors.lastname: Gandhi
mesh_terms: D000349:Africa; D006197:Hair / Q000737:chemistry*; D006801:Humans; D010349:Patient Compliance; D010919:Placebos; D065129:Pre-Exposure Prophylaxis
chemical_list: D010919:Placebos