Antiretroviral drug exposure in urethral and glans surface sampling of the penis

• Type of Material: Article
• Authors: Richard E Haaland, Centers for Disease Control and Prevention, Atlanta; Jeffrey Fountain, Centers for Disease Control and Prevention, Atlanta; Chuong Dinh, Centers for Disease Control and Prevention, Atlanta; Davis L Lupo, Centers for Disease Control and Prevention, Atlanta; Amy Martin, Centers for Disease Control and Prevention, Atlanta; Christopher Conway-Washington, Emory University; LaShonda Hall, Emory University; Colleen Kelley, Emory University; Gerardo Garcia-Lerma, Centers for Disease Control and Prevention, Atlanta; Walid Heneine, Centers for Disease Control and Prevention, Atlanta
• Language: English
• Date: 2021-05-19
• Publisher: OXFORD UNIV PRESS
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2021, Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy 2021. This work is written by (a) US Government employee(s) and is in the public domain in the US.
• Final Published Version (URL): http://dx.doi.org/10.1093/jac/dkab155
• Title of Journal or Parent Work: JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
• Volume: 76
• Issue: 9
• Start Page: 2368
• End Page: 2374
• Grant/Funding Information: This study was supported by internal funding from the United States Centers for Disease Control and Prevention.
• Keywords: EMTRICITABINE; Life Sciences & Biomedicine; HETEROSEXUAL HIV TRANSMISSION; Infectious Diseases; PREVENTION; PROTECTS MACAQUES; PHARMACOKINETICS; Microbiology; URINE; PREEXPOSURE PROPHYLAXIS; Pharmacology & Pharmacy; MEN; MALE CIRCUMCISION; TENOFOVIR ALAFENAMIDE; Science & Technology

Abstract

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, <LOD-328 ng/swab; darunavir 6 ng/swab, <LOD-149 ng/swab). Estimated peak urethral secretion emtricitabine and darunavir concentrations are between 10 and 20 μg/mL, similar to rectal secretions, 4-fold greater than in plasma, but 2-fold lower than in urine. Tenofovir and elvitegravir were detected on less than 20% of urethral or glans swabs collected within 24 h of dosing. 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.