Background: Increased cardiovascular (CV) risk persists among patients with treated HIV disease, and chronic immune activation is thought to contribute to this excess risk. Carotid intima-media thickness (CIMT) assesses atherosclerotic burden and predicts future CV events. We studied the immunologic correlates of CIMT in patients on ART with suppressed viral load (VL).
Methods: Cryopreserved mononuclear cells and plasma from the SCOPE study were used to evaluate T-cell and monocyte activation by flow cytometry and soluble markers of inflammation/coagulation by ELISA-based methods. CIMT was measured by high resolution ultrasound. Mean CIMT was calculated as the average of 12 segments (near and far wall of the common, internal, and bifurcation region of the right and left carotid arteries). Plaque was defined as a focal region of IMT>1.5mm. Associations between CIMT and immunologic markers were assessed by Spearman’s rank correlation and multivariate regression adjusting for traditional CV risk factors and CD4 count. Associations between the presence of plaque and immunologic markers were evaluated by Wilcoxon test.
Results: Participants (N=132) were on ART with VL <75 copies/mL, 93% male, 67% Caucasian. The median age was 48 yrs, 32% were on anti-hypertensive drugs, 41% were on cholesterol lowering drugs, 7% had diabetes, 7% had CVD and 26% were smokers. The median CD4 was 525 cells/µL. The mean CIMT was 1.04 mm and plaque was present in 54% of patients.
In multivariate regression adjusting for traditional CV risk factors and CD4 count, higher levels of plasma IL-6 (P<0.01) and CCR5 expression on monocytes (P<0.01) were associated with thicker common carotid-IMT. In addition, higher levels of plasma IL-6 (P=0.03), and higher % of CD57+ cells in CD28-CD8+ T cells (P=0.04) were correlated with thicker mean-CIMT.
Levels of D-dimer, CRP, sCD14, sCD163, HLA-DR+CD38+CD8+T cells and CD16+ monocytes were not associated with common carotid or mean CIMT or plaque after adjusting for traditional CV risk factors and CD4 count.
Conclusions: In patients on ART with suppressed VL, higher plasma IL6 and CCR5 expression on monocytes and higher % of CD57+ cells in CD28-CD8+T cells were independently associated with thicker CIMT after adjusting for CVD risk factors and CD4 count. Dysfunction of innate immune cells and CD8 T cell senescence likely contribute to atherosclerosis in the setting of treated and suppressed HIV.