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Effects of HIV viremia on the gastrointestinal microbiome of young MSM.

ABSTRACT: OBJECTIVE:We employed a high-dimensional covariate adjustment method in microbiome analysis to better control for behavioural and clinical confounders, and in doing so examine the effects of HIV on the rectal microbiome. DESIGN:Three hundred and eighty-three MSM were grouped into four HIV viremia categories: HIV negative (n?=?200), HIV-positive undetectable (HIV RNA??200?copies/ml; n?=?45). METHODS:We performed 16S rRNA gene sequencing on rectal swab samples and used inverse probability of treatment-weighted marginal structural models to examine differences in microbial composition by HIV viremia category. RESULTS:HIV viremia explained a significant amount of variability in microbial composition in both unadjusted and covariate-adjusted analyses (R?=?0.011, P?=?0.02). Alterations in bacterial taxa were more apparent with increasing viremia. Relative to the HIV-negative group, HIV-positive undetectable participants showed depletions in Brachyspira, Campylobacter and Parasutterella, while suppressed participants demonstrated depletions in Barnesiella, Brachyspira and Helicobacter. The microbial signature of viremic men was most distinct, showing enrichment in inflammatory genera Peptoniphilus, Porphyromonas and Prevotella and depletion of Bacteroides, Brachyspira and Faecalibacterium, among others. CONCLUSION:Our study shows that, after accounting for the influence of multiple confounding factors, HIV is associated with dysbiosis in the gastrointestinal microbiome in a dose-dependent manner. This analytic approach may allow for better identification of true microbial associations by limiting the effects of confounding, and thus improve comparability across future studies.

SUBMITTER: Cook RR

PROVIDER: S-EPMC6422698 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Effects of HIV viremia on the gastrointestinal microbiome of young MSM.

Cook Ryan R RR Fulcher Jennifer A JA Tobin Nicole H NH Li Fan F Lee David D Javanbakht Marjan M Brookmeyer Ron R Shoptaw Steve S Bolan Robert R Aldrovandi Grace M GM Gorbach Pamina M PM

AIDS (London, England) 20190401 5

<h4>Objective</h4>We employed a high-dimensional covariate adjustment method in microbiome analysis to better control for behavioural and clinical confounders, and in doing so examine the effects of HIV on the rectal microbiome.<h4>Design</h4>Three hundred and eighty-three MSM were grouped into four HIV viremia categories: HIV negative (n = 200), HIV-positive undetectable (HIV RNA < 20 copies/ml; n = 66), HIV-positive suppressed (RNA 20-200 copies/ml; n = 72) and HIV-positive viremic (RNA > 200 ...[more]

PMID: 30649052

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Project description:BackgroundHIV disproportionately impacts young, black men who have sex with men (YBMSM) who experience disparities across the HIV care continuum. A more nuanced understanding of facilitators and barriers to engagement in care, missed visits, antiretroviral uptake, adherence and viral suppression could improve care and intervention design.MethodsA randomized controlled trial of an online intervention, healthMpowerment, enrolled 465 YBMSM (18-30 years); 193 identified as HIV-positive. Bivariable and multivariable analyses of baseline data explored predictors of: engagement in care, missed visits, antiretroviral uptake, self-reported adherence, and viral suppression.ResultsMean age was 24.9 years; most identified as gay (71.0%) and were receiving HIV care (89.1%). Among those in care, 52.1% reported no missed visits in the past 12 months, 41 (24.6%) reported one missed visit, and 39 (23.4%) reported two or more. Having insurance (prevalence odds ratio [POR] 4.5; 95% CI: 1.3, 15.8) and provider self-efficacy (POR 20.1; 95% CI: 6.1, 64.1) were associated with being in care. Those with a college degree (POR 9.1; 95% CI: 1.9, 45.2) and no recent marijuana (POR 2.6; 95% CI: 1.2, 5.6) or methamphetamine use (POR 5.4; 95% CI: 1.0, 28.5) were less likely to miss visits. Most (n = 153, 84.1%) had been prescribed antiretroviral therapy. A majority of participants (70.8%) reported ?90% adherence; those with depressive symptoms had 4.7 times the odds of reporting adherence <90% (95% CI: 1.65, 13.37). Of participants who reported viral load testing in the past six months, 65% (n = 102) reported an undetectable viral load. Disclosure to sex partners was associated with viral suppression (POR 6.0; 95% CI: 1.6, 22.4).ConclusionsMulti-level facilitators and barriers to engagement across the continuum of care were identified in this sample of YBMSM. Understanding the distinct needs of YBMSM at each stage of the continuum and addressing them through tailored approaches is critical for long term success in care.

Project description:BackgroundMen who have sex with men (MSM) have been disproportionately affected by HIV-1 since the beginning of the AIDS pandemic, particularly in the USA and Europe. Compared to men who have sex with women (MSW), MSM have a distinct fecal microbiome regardless of HIV-1 infection. However, it is unclear whether the MSM-associated gut microbiome affects the susceptibility and progression of HIV-1 infection. We studied fecal microbiome profiles, short-chain fatty acids, and blood plasma inflammatory cytokines of 109 HIV-1 seroconverters (SC) from the early, 1984-1985 phase of the HIV-1 pandemic in the Multicenter AIDS Cohort Study (MACS) before and after HIV-1 infection compared to 156 HIV-1-negative MACS MSM (negative controls [NC]).ResultsWe found that family Succinivibrionaceae, S24-7, Mogibacteriaceae, Coriobacteriaceae, and Erysipelotrichaceae were significantly higher (p<0.05), whereas Odoribacteraceae, Verucomicrobiaceae, Bacteroidaceae, Barnesiellaceae, and Rikenellaceae were significantly lower (p<0.05), in SC before HIV-1 infection compared to NC. At the species level, Prevotella stercorea, Eubacterium biforme, and Collinsella aerofaciens were significantly higher (p<0.05), and Eubacterium dolichum, Desulfovibrio D168, Alistipes onderdonkii, Ruminococcus torques, Bacteroides fragilis, Bacteroides caccae, Alistipes putredinis, Akkermansia muciniphila, Bacteroides uniformis, and Bacteroides ovatus were significantly lower (p<0.05) in SC before HIV-1 infection compared to NC. After HIV-1 infection, family Prevotellaceae and Victivallaceae and species Bacteroides fragilis and Eubacterium cylindroides were significantly higher (p<0.05) in SC who developed AIDS within 5 years compared to the SC who were AIDS free for more than 10 years without antiretroviral therapy (ART). In addition, family Victivallaceae and species Prevotella stercorea, Coprococcus eutactus, and Butyrivibrio crossotus were significantly higher (p<0.05) and Gemmiger formicilis and Blautia obeum were significantly lower (p<0.05) after HIV-1 infection in SC who developed AIDS within 5-10 years compared to the SC who were AIDS-free for more than 10 years without ART. Furthermore, plasma inflammatory cytokine levels of sCD14, sCD163, interleukin 6, and lipopolysaccharide binding protein were significantly higher in SC with p<0.05 before HIV-1 infection compared to NC.ConclusionsOur results suggest that pathogenic changes in the gut microbiome were present in MSM several months prior to infection with HIV-1 in the early phase of the AIDS pandemic in the USA. This was associated with increased inflammatory biomarkers in the blood and risk for development of AIDS. Video abstract.

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Effects of HIV viremia on the gastrointestinal microbiome of young MSM.

Publications

Effects of HIV viremia on the gastrointestinal microbiome of young MSM.

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