Impact of vaginal microbiome communities on HIV antiretroviral-based pre-exposure prophylaxis (PrEP) drug metabolism.

Autor: Cheu RK; Department of Pharmaceutics, University of Washington, Seattle, Washington, United States of America.; Washington National Primate Research Center, University of Washington, Seattle, Washington, United States of America.; Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida, United States of America., Gustin AT; Department of Pharmaceutics, University of Washington, Seattle, Washington, United States of America.; Washington National Primate Research Center, University of Washington, Seattle, Washington, United States of America.; Division of Surgical Outcomes and Precision Medicine Research, Department of Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America., Lee C; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States of America., Schifanella L; Division of Surgical Outcomes and Precision Medicine Research, Department of Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America., Miller CJ; Department of Pharmaceutics, University of Washington, Seattle, Washington, United States of America.; Washington National Primate Research Center, University of Washington, Seattle, Washington, United States of America.; Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida, United States of America., Ha A; Department of Pharmaceutics, University of Washington, Seattle, Washington, United States of America.; Washington National Primate Research Center, University of Washington, Seattle, Washington, United States of America., Kim C; Department of Pharmaceutics, University of Washington, Seattle, Washington, United States of America.; Washington National Primate Research Center, University of Washington, Seattle, Washington, United States of America., Rodriguez VJ; Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States of America.; Department of Psychology, University of Georgia, Athens, Georgia, United States of America., Fischl M; Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States of America., Burgener AD; Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada.; Center for Global Health and Disease, Case Western Reserve University, Cleveland, Ohio, United States of America., Arnold KB; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States of America., Alcaide ML; Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States of America., Klatt NR; Department of Pharmaceutics, University of Washington, Seattle, Washington, United States of America.; Washington National Primate Research Center, University of Washington, Seattle, Washington, United States of America.; Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida, United States of America.; Division of Surgical Outcomes and Precision Medicine Research, Department of Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2020 Dec 03; Vol. 16 (12), pp. e1009024. Date of Electronic Publication: 2020 Dec 03 (Print Publication: 2020).
DOI: 10.1371/journal.ppat.1009024
Abstrakt: Despite the efficacy of antiretroviral-based pre-exposure prophylactics (PrEP) in men who have sex with men, studies in women have produced widely varying outcomes. Recent evidence demonstrates that vaginal microbial communities are associated with increased HIV acquisition risk and may impact PrEP efficacy. Here, we investigate the mechanisms underlying how vaginal bacteria alter PrEP drug levels and impact HIV infection rates ex vivo. Using cervicovaginal lavages (CVLs) from women with or without bacterial vaginosis (BV), we identified microbial metabolism of PrEP drugs in BV samples through LC-MS/MS analysis of soluble drug levels and metabolite formation in dual T-cell cultures. CVL samples were assessed for microbiome analysis using sequencing of bacterial 16S rRNA genes. We also observed non-Lactobacillus bacteria that are associated with BV may potentially impact PrEP efficacy through increased HIV infection rates in co-cultures containing Lactobacillus or BV bacteria, PrEP drugs, CEM-GFP cells, and HIV-1LAI virus. Finally, we used these data to develop a novel predictive mathematical simulation modeling system to predict these drug interactions for future trials. These studies demonstrate how dysbiotic vaginal microbiota may impact PrEP drugs and provides evidence linking vaginal bacteria to PrEP efficacy in women.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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