# 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

## TL;DR

This study shows that immune dysregulation in people with HIV is linked to increased thickness of artery walls, a sign of early heart disease.

## Contribution

The study identifies a novel association between CD4+ cell count nadir and CD4/CD8 ratio with carotid intima-media thickness in people living with HIV.

## Key findings

- Lower CD4+ cell count nadir is associated with increased carotid intima-media thickness (cIMT) severity.
- A CD4/CD8 ratio ≥1.0 combined with low CD4+ nadir is linked to higher odds of severe cIMT.
- Immune dysregulation markers are independently associated with subclinical atherosclerosis in HIV patients.

## Abstract

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.