Impact of antimicrobials on penile HIV susceptibility and immunology in uncircumcised men: A randomized phase 1/2 clinical trial

Ronald M. Galiwango; Brenda Okech; Daniel E. Park; Lane Buchanan; Zhongtian Shao; Bernard Bagaya; Juliet Mpendo; Vineet Joag; Sergey Yegorov; Annet Nanvubya; Victoria M. Biribawa; Teddy Namatovu; Charles Kato; Barbara Kawoozo; Ali Ssetaala; Moses Muwanga; Maliha Aziz; Tony Pham; Sanja Huibner; Aaron A.R. Tobian; Cindy M. Liu; Jessica L. Prodger; Rupert Kaul

Cell Reports Medicine (Sep 2024)

Impact of antimicrobials on penile HIV susceptibility and immunology in uncircumcised men: A randomized phase 1/2 clinical trial

Ronald M. Galiwango,
Brenda Okech,
Daniel E. Park,
Lane Buchanan,
Zhongtian Shao,
Bernard Bagaya,
Juliet Mpendo,
Vineet Joag,
Sergey Yegorov,
Annet Nanvubya,
Victoria M. Biribawa,
Teddy Namatovu,
Charles Kato,
Barbara Kawoozo,
Ali Ssetaala,
Moses Muwanga,
Maliha Aziz,
Tony Pham,
Sanja Huibner,
Aaron A.R. Tobian,
Cindy M. Liu,
Jessica L. Prodger,
Rupert Kaul

Affiliations

Ronald M. Galiwango: Departments of Medicine and Immunology, University of Toronto, Toronto, ON M5S1A8, Canada
Brenda Okech: UVRI-IAVI HIV Vaccine Program, Entebbe, Uganda
Daniel E. Park: Department of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington University, Washington, DC 20052, USA
Lane Buchanan: Departments of Microbiology and Immunology and Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University, London, ON N6A3K7, Canada
Zhongtian Shao: Departments of Microbiology and Immunology and Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University, London, ON N6A3K7, Canada
Bernard Bagaya: UVRI-IAVI HIV Vaccine Program, Entebbe, Uganda; Department of Microbiology, Makerere University College of Health Sciences, Kampala, Uganda
Juliet Mpendo: UVRI-IAVI HIV Vaccine Program, Entebbe, Uganda
Vineet Joag: Departments of Medicine and Immunology, University of Toronto, Toronto, ON M5S1A8, Canada; Centre for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
Sergey Yegorov: Departments of Medicine and Immunology, University of Toronto, Toronto, ON M5S1A8, Canada; McMaster University, Institute for Infectious Disease Research, Guelph, ON L8S4L8, Canada
Annet Nanvubya: UVRI-IAVI HIV Vaccine Program, Entebbe, Uganda
Victoria M. Biribawa: UVRI-IAVI HIV Vaccine Program, Entebbe, Uganda
Teddy Namatovu: UVRI-IAVI HIV Vaccine Program, Entebbe, Uganda
Charles Kato: UVRI-IAVI HIV Vaccine Program, Entebbe, Uganda
Barbara Kawoozo: UVRI-IAVI HIV Vaccine Program, Entebbe, Uganda
Ali Ssetaala: UVRI-IAVI HIV Vaccine Program, Entebbe, Uganda
Moses Muwanga: Entebbe General Hospital, Entebbe, Uganda
Maliha Aziz: Department of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington University, Washington, DC 20052, USA
Tony Pham: Department of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington University, Washington, DC 20052, USA
Sanja Huibner: Departments of Medicine and Immunology, University of Toronto, Toronto, ON M5S1A8, Canada
Aaron A.R. Tobian: Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
Cindy M. Liu: Department of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington University, Washington, DC 20052, USA
Jessica L. Prodger: Departments of Microbiology and Immunology and Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University, London, ON N6A3K7, Canada
Rupert Kaul: Departments of Medicine and Immunology, University of Toronto, Toronto, ON M5S1A8, Canada; Department of Medicine, University Health Network, Toronto, ON M5G2C4, Canada; Corresponding author

Journal volume & issue: Vol. 5, no. 9
p. 101705

Abstract

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Summary: 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.

Published in Cell Reports Medicine

ISSN: 2666-3791 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Medicine (General)
Website: https://www.cell.com/cell-reports-medicine

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