The Role of Immune Dysregulation Markers in Cardiovascular Risk of People Living with HIV: Association Among Intima Media Changes, CD4/CD8 Ratio, and CD4+ Cell Count Nadir

HIV infection can promote persistent immune activation and endothelial dysfunction, contributing to atherosclerosis. Carotid intima-media thickness (cIMT) is an established marker of subclinical atherosclerosis. We evaluated the association between cIMT severity and two routinely available markers of immune dysregulation (CD4/CD8 ratio and nadir CD4+ cell count) in people living with HIV (PLWH). We conducted an Italian multicenter cross-sectional study including 1148 PLWH who underwent carotid color Doppler ultrasound. We classified cIMT as ≤0.9, 1.0-1.4, or >1.4 mm and analyzed these categories using multinomial logistic regression, reporting adjusted odds ratios (aORs) with 95% confidence intervals (CIs). We adjusted models for age, sex, BMI, HIV acquisition risk factor, hypertension, diabetes, dyslipidemia/statin use, triglycerides, integrase inhibitor use, and ART duration. cIMT was ≤0.9 mm in 615 (53.6%) participants, 1.0-1.4 mm in 379 (33.0%), and >1.4 mm in 154 (13.4%). Using nadir CD4+ ≥ 200 cells/µL and CD4/CD8 ≥ 1.0 as reference, PLWH with nadir CD4+ < 200 and CD4/CD8 ≥ 1.0 had higher odds of cIMT 1.0-1.4 mm (aOR 1.66, 95% CI 1.02-2.69) and >1.4 mm (aOR 3.45, 95% CI 1.68-7.07). In conclusion, CD4+ nadir and this combined pattern were associated with greater cIMT severity, supporting a role for immune dysregulation in subclinical atherosclerosis.