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Impact of antimicrobials on penile HIV susceptibility and immunology in uncircumcised men: A randomized phase 1/2 clinical trial.
Galiwango, Ronald M; Okech, Brenda; Park, Daniel E; Buchanan, Lane; Shao, Zhongtian; Bagaya, Bernard; Mpendo, Juliet; Joag, Vineet; Yegorov, Sergey; Nanvubya, Annet; Biribawa, Victoria M; Namatovu, Teddy; Kato, Charles; Kawoozo, Barbara; Ssetaala, Ali; Muwanga, Moses; Aziz, Maliha; Pham, Tony; Huibner, Sanja; Tobian, Aaron A R; Liu, Cindy M; Prodger, Jessica L; Kaul, Rupert.
Affiliation
  • Galiwango RM; Departments of Medicine and Immunology, University of Toronto, Toronto, ON M5S1A8, Canada.
  • Okech B; UVRI-IAVI HIV Vaccine Program, Entebbe, Uganda.
  • Park DE; Department of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington University, Washington, DC 20052, USA.
  • Buchanan L; Departments of Microbiology and Immunology and Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University, London, ON N6A3K7, Canada.
  • Shao Z; Departments of Microbiology and Immunology and Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University, London, ON N6A3K7, Canada.
  • Bagaya B; UVRI-IAVI HIV Vaccine Program, Entebbe, Uganda; Department of Microbiology, Makerere University College of Health Sciences, Kampala, Uganda.
  • Mpendo J; UVRI-IAVI HIV Vaccine Program, Entebbe, Uganda.
  • Joag V; Departments of Medicine and Immunology, University of Toronto, Toronto, ON M5S1A8, Canada; Centre for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
  • Yegorov S; Departments of Medicine and Immunology, University of Toronto, Toronto, ON M5S1A8, Canada; McMaster University, Institute for Infectious Disease Research, Guelph, ON L8S4L8, Canada.
  • Nanvubya A; UVRI-IAVI HIV Vaccine Program, Entebbe, Uganda.
  • Biribawa VM; UVRI-IAVI HIV Vaccine Program, Entebbe, Uganda.
  • Namatovu T; UVRI-IAVI HIV Vaccine Program, Entebbe, Uganda.
  • Kato C; UVRI-IAVI HIV Vaccine Program, Entebbe, Uganda.
  • Kawoozo B; UVRI-IAVI HIV Vaccine Program, Entebbe, Uganda.
  • Ssetaala A; UVRI-IAVI HIV Vaccine Program, Entebbe, Uganda.
  • Muwanga M; Entebbe General Hospital, Entebbe, Uganda.
  • Aziz M; Department of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington University, Washington, DC 20052, USA.
  • Pham T; Department of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington University, Washington, DC 20052, USA.
  • Huibner S; Departments of Medicine and Immunology, University of Toronto, Toronto, ON M5S1A8, Canada.
  • Tobian AAR; Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
  • Liu CM; Department of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington University, Washington, DC 20052, USA.
  • Prodger JL; Departments of Microbiology and Immunology and Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University, London, ON N6A3K7, Canada.
  • Kaul R; Departments of Medicine and Immunology, University of Toronto, Toronto, ON M5S1A8, Canada; Department of Medicine, University Health Network, Toronto, ON M5G2C4, Canada. Electronic address: rupert.kaul@utoronto.ca.
Cell Rep Med ; 5(9): 101705, 2024 Sep 17.
Article in En | MEDLINE | ID: mdl-39214083
ABSTRACT
Within the penile microbiome, bacteria associated with seroconversion, immunology, and cells (BASIC species) enhance HIV susceptibility in heterosexual uncircumcised men by inducing foreskin inflammation and HIV target cell recruitment. This phase 1/2 clinical trial randomizes HIV-uninfected Ugandan men (n = 125) to either oral tinidazole, topical metronidazole, topical clindamycin, or topical hydrogen peroxide to define impact on ex vivo foreskin HIV susceptibility, penile immunology, and BASIC species density. Antimicrobials are well tolerated, and 116 (93%) participants complete the protocol. Topical metronidazole and oral tinidazole reduce the inner foreskin tissue density of HIV-susceptible CD4+ T cells (predefined primary endpoint). Antimicrobials also have varying but substantial effects on reducing prepuce inflammation and BASIC species density, reducing density of foreskin T cell subsets, and increasing foreskin epithelial integrity. Immune alterations correlate strongly with changes in the abundance of BASIC species. Clinical interventions targeting the penile microbiota, particularly topical metronidazole, may reduce HIV susceptibility in uncircumcised men.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Penis / HIV Infections Limits: Adult / Humans / Male Country/Region as subject: Africa Language: En Journal: Cell Rep Med Year: 2024 Document type: Article Affiliation country: Canada Country of publication: United States
Fulltext
Add to My VHL
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Penis / HIV Infections Limits: Adult / Humans / Male Country/Region as subject: Africa Language: En Journal: Cell Rep Med Year: 2024 Document type: Article Affiliation country: Canada Country of publication: United States