Gut-heart immuno-metabolic disruption associated with inflammaging and subclinical coronary artery disease in people with HIV on antiretroviral therapy

BACKGROUND: Despite antiretroviral therapy (ART), people with HIV (PWH) face immunological ageing and accelerated comorbidities including coronary artery disease (CAD). Gut mucosal damage, chronic inflammation, and Tryptophan (Trp) catabolism into Kynurenine (Kyn) by indoleamine 2,3-dioxygenase (IDO), are associated with HIV disease progression and atherosclerosis. Thus, we comprehensively assessed the interplay between these perturbations in PWH with subclinical CAD under ART. METHODS: Plasma levels of inflammatory mediators, Trp metabolites, and immune cell subset phenotyping were assessed on blood specimens from PWH and HIV seronegative participants with or without CAD diagnosed by cardiac computed tomography angiography from the Canadian HIV Aging Cohort Study. RESULTS: CD4 and CD8 T-cells, while T-cell and regulatory T-cells (Treg) atheroprotective CD73-expressing subsets were decreased in PWH. CONCLUSIONS: In PWH, subclinical CAD is associated with a distinctive gut-heart immuno-metabolic feature and inflammaging characterized by elevated plasma markers of gut mucosal damage, increased IFN-γ levels and IDO pathway activity, and altered monocyte and T-cell subsets.