Immune-inflammatory profiles, coronary artery disease, and peripheral artery disease in people with HIV.

BACKGROUND AND AIMS: People with HIV (PWH) have high risk of coronary (CAD) and peripheral (PAD) artery disease independent of traditional risk factors. Single immune-inflammatory biomarkers provide limited insight into disease risk and phenotypes, whereas integrative profiling may reveal novel mechanisms. Here we investigated associations between immune-inflammatory profiles, CAD, and PAD in PWH.

METHODS

We included PWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study with undetectable HIV RNA and measurements of 25 immune-inflammatory biomarkers. Participants underwent coronary computed tomography angiography and ankle-brachial index (ABI) measurements to assess for CAD and PAD. Unsupervised hierarchical clustering on principal components grouped participants by immune-inflammatory clusters, and we assessed their associations with CAD and PAD.

RESULTS

Among 651 PWH, we identified three immune-inflammatory clusters: one with low senescent T cell proportions; one with low concentrations of inflammation, innate activation, and endothelial dysfunction markers (reference cluster); and one with high senescent T cell proportions and concentrations of inflammation, innate activation, and endothelial dysfunction markers (high inflammation cluster). The high inflammation cluster was associated with obstructive CAD (adjusted OR 2.42 [95% CI: 1.06; 5.33]), higher lipid-rich plaque volumes (adjusted β = 8.47 [95% 0.84; 16.1] μL), and lower ABI (adjusted β = -0.07 [95% CI: -0.13;-0.01]) among those with PAD compared to the reference cluster, after adjustment for age, sex, smoking, hypertension, diabetes, and dyslipidaemia.

CONCLUSIONS

An immune-inflammatory profile characterised by T cell senescence, inflammation, innate activation, and endothelial dysfunction was associated with high-risk CAD severity, highlighting immunopathogenic pathways associated with atherosclerosis in PWH.