Immuno-virologic factors involved in cardiovascular disease (CVD) risk in HIV-infected, art-treated individuals

Background: HIV-infected patients undergoing ART have a greater burden of subclinical and clinical atherosclerotic disease compared to general population. Recent evidences suggest a direct role of HIV infection in the pathogenesis of cardio-vascular diseases (CVD). However, it is still unclear whether chronic inflammation, endothelial cell activation, and the activation of the peculiar cytokine networks characteristic of HIV infection are associated with the increased prevalence of atherosclerosis disease. Objective: Aim of this study was to evaluate possible associations between inflammation, metabolic factors and endothelial alterations in HIV- infection. Materials and Methods: Sixty-eight HIV-infected patients (45 ART-treated and 23 naive individuals) were enrolled in the study. Fifty % of patients in both groups had a high cardiovascular risk (Framingham value >20%). Echo-Doppler (carotid intima media thickness, IMT), the expression of adhesion and activation molecules on circulating immune cells, plasmatic inflammatory and metabolic indexes, as well as plasmatic pro- and anti-inflammatory cytokines and chemokines and soluble adhesion molecules were cross-sectionally evaluated. A multivariate analysis (corrected for age, CD4 nadir, and the Framingham value) was used. Results: As compared to naive patients, ART-treated individuals showed: 1) significantly increased IMT (p= 0.007); 2) reduced hCRP levels (p= 0.017); 3) lower plasmatic IL6, TNFalpha, sICAM1, and sVCAM1 levels (p= 0.0036; p< 0.001; p= 0.011; p= 0.028); 4) higher percentages of CD44-, CD11a-, CD62L- and CD49d-expressing CD4 T cells (p< 0.001; p= 0.001; p= 0.006; p= 0.03); 5) lower percentages of CD86/CD14 cells (p= 0.003). No significant differences were observed in TLR2- and TLR4-expressing CD14 cell and in plasma LPS levels. Conclusions: ART plays a critical role in the pathogenesis of atherosclerotic plaques in HIV-infected patients. Classical inflammatory parameters (hCRP, IL-6, etc) are nevertheless reduced in these patients, suggesting a non-inflammatory etiology of atherosclerosis in ART individuals. Atherosclerosis in HIV-infected patients may be due to direct toxic effects of ART.