Urine Emtricitabine and Tenofovir Concentrations Provide Markers of Recent Antiretroviral Drug Exposure Among HIV-Negative Men Who Have Sex With Men

• Authors: Richard E. Haaland, Centers for Disease Control and Prevention; Amy Martin, Centers for Disease Control and Prevention; Tamee Livermont, Centers for Disease Control and Prevention; Jeffrey Fountain, Centers for Disease Control and Prevention; Dinh Chuong, Centers for Disease Control and Prevention; Angela Holder, Centers for Disease Control and Prevention; Lindsey D. Lupo, Centers for Disease Control and Prevention; LaShonda Hall, Emory University; Christopher Conway-Washington, Emory University; Colleen Kelley, Emory University
• Journal Title: JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
• Volume: Volume 82, Number 3
• Publisher: LIPPINCOTT WILLIAMS & WILKINS | 2019-11-01, Pages 252-256
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1097/QAI.0000000000002133
• Subjects: Health Sciences, Immunology; Biology, Virology; Health Sciences, Public Health
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; Infectious Diseases; antiretroviral agents; point-of-care testing; PrEP; urine; men who have sex with men; HIV; DRIED BLOOD SPOTS; PREEXPOSURE PROPHYLAXIS; ADHERENCE; PREP; DIPHOSPHATE; PREVENTION; ASSAY; HAIR; ALAFENAMIDE; INFECTION

Abstract

Background:Urine provides a minimally invasive specimen that may allow for development of rapid tests to detect antiretroviral drugs and provide opportunities to improve individual adherence. This study sought to determine whether urine could provide a biomarker of adherence for currently approved pre-exposure prophylaxis and HIV treatment regimens.Methods:Urine and blood were collected from 34 HIV-negative men who have sex with men aged 18-49 years, enrolled in a clinical trial comparing 2 antiretroviral regimens. Specimens were collected 4 and 24 hours after a single oral dose of tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) (n = 10) or tenofovir alafenamide (TAF)/FTC/cobicistat (COBI)/elvitegravir (EVG) (n = 8), or after 4 and 10 days of daily oral TDF/FTC (n = 9) or TAF/FTC/COBI/EVG (n = 7). Tenofovir (TFV), FTC, and EVG were measured by high-performance liquid chromatography-mass spectrometry.Results:Median urine FTC concentrations at 4 and 24 hours were similar between men receiving TDF/FTC (4 hours 147 μg/mL; 24 hours 10 μg/mL) and men receiving TAF/FTC/COBI/EVG (4 hours 333 μg/mL, P = 0.173; 24 hours 13 μg/mL, P = 0.681). Median urine TFV concentrations were lower among men receiving TAF/FTC/COBI/EVG (4 hours 1.2 μg/mL; 24 hours 0.8 μg/mL) compared with men receiving TDF/FTC (4 hours 17 μg/mL, P < 0.001; 24 hours 7 μg/mL, P = 0.001). Urine TFV concentrations remained reduced among men receiving TAF/FTC/COBI/EVG compared with men receiving TDF/FTC after daily dosing. EVG was not consistently measurable in urine.Conclusions:High urine FTC and TFV concentrations could provide an indication of adherence to daily oral dosing with TDF or TAF-based regimens used for treatment and prevention.