Serum tryptophan-derived quinolinate and indole-3-acetate are associated with carotid intima-media thickness and its evolution in HIV-infected treated adults

Background HIV-infected individuals undergoing effective antiretroviral therapy (ART) present an increased risk of atherosclerotic cardiovascular disease. We identified serum metabolites associated with carotid intima-media-thickness (c-IMT) and its evolution. Methods 143 hydrophilic serum metabolites were measured by ultra-performance-liquid-chromatography coupled to high-resolution mass-spectrometry in 49 HIV+ART+, 48 HIV+ART-naïve, and 50 HIV-negative age-matched, never-smoking, male triads. Metabolites differentially altered between groups (“features”) were defined as having a Benjamini-Hochberg adjusted p-value 0.25 log2 absolute mean fold-change in metabolite levels. c-IMT was measured across 12 sites at inclusion in all individuals and at the carotid-artery (cca) after a median 5.1 years in 32 HIV+ART+ individuals. Difference in c-IMT (cross-sectional analysis) and slope of cca-IMT regression/progression per year (longitudinal analysis) for each log10(area) increase in metabolite level was estimated with linear regression. Results Compared to HIV-, metabolite features of HIV+ART+ were increased N6,N6,N6-trimethyl-L-lysine and decreased ferulate and 5-hydroxy-L-tryptophan; while features of HIV+ART-naïve were increased malate, kynurenine, 2-oxoglutarate, and indole-3-acetate and decreased succinate and 5-hydroxy-L-tryptophan. In HIV+ART+ individuals, quinolinate and/or indole-3-acetate were positively associated with c-IMT (p Conclusion In these highly-selected HIV-positive ART-controlled males, two novel metabolites derived from tryptophan catabolism, indole-3-acetate and quinolinate, were associated with c-IMT and its progression.