Search

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.

Background: HIV exposure to penile tissues provides a risk of acquisition among men, yet studies evaluating penile antiretroviral (ARV) drug distribution have been lacking. We measured ARVs on urethral and glans surface swabs collected following a dose of tenofovir alafenamide, emtricitabine, elvitegravir, darunavir and cobicistat.Methods: Thirty-five HIV-negative male participants provided urethral swabs, glans swabs, rectal swabs, blood and urine up to 96 h following a single dose of tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat and darunavir. ARVs were measured by liquid chromatography-mass spectrometry with a lower limit of detection (LOD) of 1 ng/swab for swabs and 10 ng/mL for plasma and urine. Concentrations are reported as median and range.Results: Urethral swab emtricitabine and darunavir concentrations peaked at 4 h for emtricitabine (36 ng/swab; 3-307 ng/swab) and 8 h for darunavir (25 ng/swab; 2-52 ng/swab). Glans swab emtricitabine and darunavir concentrations peaked 24 h after dosing (emtricitabine 14 ng/swab, Conclusions: We document ARV dosing in the urethra and on the glans surface with high drug concentrations noted for emtricitabine and darunavir and lower tenofovir and elvitegravir concentrations. Data suggest a potential protective role of urethral emtricitabine or darunavir against penile HIV acquisition. [ABSTRACT FROM AUTHOR]

Introduction: Oral pre‐exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is highly effective in preventing HIV infection among men who have sex with men (MSM). The effects of consistent personal lubricant use in the rectum on tissue PrEP drug concentrations and the rectal microbiota are unknown. We investigated rectal PrEP drug concentrations and the microbiota in MSM before and after repeated rectal application of a hyperosmolar lubricant. Methods: We randomized 60 HIV‐negative MSM to apply 4 mL of hyperosmolar rectal lubricant daily (n = 20), take daily oral TDF/FTC (n = 19), or both (n = 21) for seven days. Blood, rectal biopsies and rectal secretions were collected via rigid sigmoidoscopy before and on day 8 after product use. Tenofovir (TFV) and FTC as well as their intracellular metabolites tenofovir‐diphosphate (TFV‐DP), FTC‐triphosphate (FTC‐TP) were measured by HPLC‐mass spectrometry. Rectal mucosal microbiota was sequenced with 16S rRNA sequencing using Illumina MiSeq. Results: Seven days of lubricant application was not associated with differences in PrEP drug concentrations in rectal tissue or secretions. Lubricant use was associated with a decrease in the relative abundance of the Bacteroides genus (p = 0.01) and a non‐significant increase in the Prevotella genus (p = 0.09) in the rectum. PrEP drug concentrations in rectal tissue and secretions were not associated with microbiota composition or diversity either before or after lubricant use. Conclusions: Repeated rectal application of a hyperosmolar lubricant does not affect mucosal PrEP drug concentrations but is associated with changes in the rectal microbiome. [ABSTRACT FROM AUTHOR]