Urine emtricitabine and tenofovir concentrations provide markers of recent antiretroviral drug exposure among HIV-negative men who have sex with men.

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 mu g/mL; 24 hours 10 mu g/mL) and men receiving TAF/FTC/COBI/EVG (4 hours 333 mu g/mL, P = 0.173; 24 hours 13 mu g/mL, P = 0.681). Median urine TFV concentrations were lower among men receiving TAF/ FTC/COBI/EVG (4 hours 1.2 mu g/mL; 24 hours 0.8 mu g/mL) com pared with men receiving TDF/FTC (4 hours 17 mu g/mL, P < 0.001; 24 hours 7 mu g/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.