Comparing the Novel Method of Assessing PrEP Adherence/Exposure Using Hair Samples to Other Pharmacologic and Traditional Measures
Year: 2014
Type: article
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. 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.
Institutions: University of California, San Francisco, Kenya Medical Research Institute, University of Oxford, Massachusetts General Hospital, San Francisco Department of Public Health, Kenya AIDS Vaccine Initiative, KEMRI-Wellcome Trust Research Programme, MRC/UVRI & LSHTM Uganda Research Unit, Uganda Virus Research Institute, Gilead Sciences (United States), Johns Hopkins University, Johns Hopkins Medicine, International AIDS Vaccine Initiative
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Awards: G1344608833, G1733730776, Director's discretionary recruitment fund and contribution toward Kilifi District Hospital, The Connie Wofsy Women's HIV Study, G3726674119, G3936936596, Oxford part of Kenya MOP renewal 2010 - 2015, G647763927, G773494495, G81379742, Traineeships in AIDS Prevention Studies, Center for AIDS Prevention Studies (CAPS)
OpenAlex ID: W2006938665