Associations Between the Gut Microbiome, Inflammation, and Cardiovascular Profiles in People With Human Immunodeficiency Virus

Background. Inflammation and innate immune activation are associated with chronic human immunodeficiency virus (HIV) infection, despite effective treatment. Although gut microbiota alterations are linked to systemic inflammation, their relationship with HIV infection the relationships between the gut microbiome, inflammation, and HIV remains unclear. Methods. The HIV UPBEAT Coronary Artery Disease sub-study evaluated cardiovascular disease (CVD) in people with and without HIV. Subclinical CVD was assessed using coronary computed tomography angiography (CCTA). Thirty-four biomarkers were measured using quantitative immunoassays. Stool samples underwent 16S rRNA sequencing. Differentially abundant species were identified by analysis of compositions of microbiomes with bias correction (ANCOM-BC) and correlated to biomarkers, diet, and CCTA outcomes using Spearman correlation. Results. Among 81 participants (median age, 51 years; 73% male), people with HIV (n = 44) had higher rates of hypercholesterolemia (P < .025). Gut microbiome beta-diversity differed significantly by HIV status. Enriched Bifidobacterium pseudocatenulatum, Megamonas hypermegale, and Selenomonas ruminantium correlated with lower plaque burden, while depleted Ruminococcus bromii correlated with higher plaque burden and fat intake. Depleted Bacteroides spp and Alistepes spp correlated with elevated biomarkers (D-dimer, CD40 ligand, C-reactive protein, and interferon-gamma). Conclusions. Gut microbiota differences in people with HIV were linked to subclinical CVD, diet, and inflammation, highlighting the microbiome's role in cardiovascular risk in HIV infection.