Gilead Sciences, Inc., Foster City, California, USA.
Department of Medicine, University of California San Francisco, San Francisco, California, USA.
Eur J Immunol. 2024 Aug;54(8):e2350809. doi: 10.1002/eji.202350809. Epub 2024 May 10.
HIV infection is associated with gut dysbiosis, and microbiome variability may affect HIV control when antiretroviral therapy (ART) is stopped. The TLR7 agonist, vesatolimod, was previously associated with a modest delay in viral rebound following analytical treatment interruption in HIV controllers (HCs). Using a retrospective analysis of fecal samples from HCs treated with vesatolimod or placebo (NCT03060447), people with chronic HIV (CH; NCT02858401) or without HIV (PWOH), we examined fecal microbiome profile in HCs before/after treatment, and in CH and PWOH. Microbiome diversity and abundance were compared between groups to investigate the association between specific phyla/species, immune biomarkers, and viral outcomes during treatment interruption. Although there were no significant differences in gut microbiome diversity between people with and without HIV, HCs, and CH shared common features that distinguished them from PWOH. there was a trend toward greater microbiome diversity among HCs. Treatment with vesatolimod reduced dysbiosis in HCs. Firmicutes positively correlated with T-cell activation, while Bacteroidetes and Euryarchaeota inversely correlated with TLR7-mediated immune activation. Specific types of fecal microbiome abundance (e.g. Alistipes putredinis) positively correlated with HIV rebound. In conclusion, variability in the composition of the fecal microbiome is associated with markers of immune activation following vesatolimod treatment and ART interruption.
HIV 感染与肠道菌群失调有关，而微生物组的可变性可能会影响停止抗逆转录病毒治疗（ART）时的 HIV 控制。TLR7 激动剂，vesatolimod，之前与 HIV 控制器（HC）在分析性治疗中断后病毒反弹的适度延迟相关。使用接受 vesatolimod 或安慰剂治疗的 HC 的粪便样本的回顾性分析（NCT03060447），慢性 HIV（CH；NCT02858401）或无 HIV（PWOH）的人，我们研究了治疗前后 HC 中的粪便微生物组特征，以及 CH 和 PWOH。比较各组之间的微生物组多样性和丰度，以研究治疗中断期间特定门/种、免疫生物标志物和病毒结果之间的关联。尽管有 HIV 和无 HIV 的人之间的肠道微生物组多样性没有显著差异，但 HC 和 CH 有一些共同的特征，使它们与 PWOH 区分开来。HC 中存在微生物组多样性增加的趋势。vesatolimod 治疗可减少 HC 的肠道菌群失调。厚壁菌门与 T 细胞激活呈正相关，而拟杆菌门和广古菌门与 TLR7 介导的免疫激活呈负相关。粪便微生物组丰度的特定类型（例如 Alistipes putredinis）与 HIV 反弹呈正相关。总之，粪便微生物组组成的可变性与 vesatolimod 治疗和 ART 中断后免疫激活的标志物相关。
