HIV rebound in HIV controllers is associated with a specific fecal microbiome profile

Author:

Cai Yanhui1ORCID,Podlaha Ondrej1,Deeks Steven G.2,Brinson Cynthia3,Ramgopal Moti N.4,DeJesus Edwin5,Mills Anthony6,Shalit Peter7,Abdel‐Mohsen Mohamed8,Zhang Liao1ORCID,de Vries Christiaan R.1ORCID,Vendrame Elena1ORCID,SenGupta Devi1,Wallin Jeffrey J.1ORCID

Affiliation:

1. Gilead Sciences, Inc. Foster City California USA

2. Department of Medicine University of California San Francisco San Francisco California USA

3. Central Texas Clinical Research Austin Texas USA

4. Midway Immunology and Research Center Fort Pierce Florida USA

5. Orlando Immunology Centre Orlando Florida USA

6. Men's Health Foundation West Hollywood California USA

7. Peter Shalit MD and Associates Seattle Washington USA

8. Vaccine and Immunotherapy Center The Wistar Institute Philadelphia Pennsylvania USA

Abstract

AbstractHIV 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.

Funder

Gilead Sciences

Publisher

Wiley

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