Repeated rectal application of a hyperosmolar lubricant is associated with microbiota shifts but does not affect PrEP drug concentrations: results from a randomized trial in men who have sex with men

• Authors: Richard E Haaland, Center for Disease Control and Prevention; Jeffrey Fountain, Center for Disease Control and Prevention; Yingtian Hu, Emory University; Angela Holder, Center for Disease Control and Prevention; Chuong Dinh, Center for Disease Control and Prevention; LaShonda Hall, Emory University; Nicole A Pescatore, Emory University; Sheila Heeke, Emory University; Clyde E Hart, Center for Disease Control and Prevention; Jiahui Xu, St Jude Childrens Research Hospital; Yi-Juan Hu, Emory University; Colleen Kelley, Emory University
• Journal Title: Journal of the International AIDS Society
• Volume: Volume 21, Number 10
• Publisher: Wiley Open Access | 2018-10-31, Pages e25199-e25199
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1002/jia2.25199
• Subjects: Health Sciences, Immunology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; Infectious Diseases; lubricant; men who have sex with men; pre-exposure prophylaxis; anti-retroviral agents; HIV; gut microbiota; REVERSE-TRANSCRIPTASE INHIBITORS; NATURAL SUBSTRATE CONCENTRATIONS; BLOOD MONONUCLEAR-CELLS; PREEXPOSURE PROPHYLAXIS; PERSONAL LUBRICANTS; HIV-1 INFECTION; HIGH-RISK; TENOFOVIR; TRANSMISSION; MUCOSAL

Abstract

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.