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抗微生物药物对未行包皮环切术男性阴茎 HIV 易感性和免疫的影响：一项随机 1/2 期临床试验。

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

机构信息

Departments of Medicine and Immunology, University of Toronto, Toronto, ON M5S1A8, Canada.

UVRI-IAVI HIV Vaccine Program, Entebbe, Uganda.

出版信息

Cell Rep Med. 2024 Sep 17;5(9):101705. doi: 10.1016/j.xcrm.2024.101705. Epub 2024 Aug 29.

DOI:10.1016/j.xcrm.2024.101705
PMID:39214083
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11536468/
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.

摘要

在阴茎微生物组中，与血清转换、免疫学和细胞相关的细菌（BASIC 物种）通过诱导包皮炎症和 HIV 靶细胞募集，增加未割包皮的异性恋男性感染 HIV 的易感性。这项 1/2 期临床试验将感染 HIV 的乌干达男性（n=125）随机分为口服替硝唑、局部甲硝唑、局部克林霉素或局部过氧化氢组，以确定其对体外包皮 HIV 易感性、阴茎免疫学和 BASIC 物种密度的影响。抗菌药物耐受性良好，116 名（93%）参与者完成了方案。局部甲硝唑和口服替硝唑降低了 HIV 易感 CD4 T 细胞的内包皮组织密度（预先定义的主要终点）。抗菌药物还对减少包皮炎症和 BASIC 物种密度、减少包皮 T 细胞亚群密度以及增加包皮上皮完整性有不同但显著的影响。免疫改变与 BASIC 物种丰度的变化密切相关。针对阴茎微生物群的临床干预，特别是局部甲硝唑，可能会降低未割包皮男性感染 HIV 的易感性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cce/11536468/0d6caf2b793f/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cce/11536468/263ecb005496/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cce/11536468/25a0eb3a2eca/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cce/11536468/64f881bf1d79/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cce/11536468/33b47d6f0b11/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cce/11536468/1453ecbd08bd/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cce/11536468/75743f906485/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cce/11536468/0d6caf2b793f/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cce/11536468/263ecb005496/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cce/11536468/25a0eb3a2eca/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cce/11536468/64f881bf1d79/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cce/11536468/33b47d6f0b11/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cce/11536468/1453ecbd08bd/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cce/11536468/75743f906485/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cce/11536468/0d6caf2b793f/gr6.jpg

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