Increased Carotid Intima-Media Thickness Associated with Antibody Responses to Varicella-Zoster Virus and Cytomegalovirus in HIV-Infected Patients

Objective: We investigated the relationship of the Herpesviridiae with inflammation and subclinical atherosclerosis in HIVinfected patients. Methods: Prospective study including virologically suppressed HIV-infected patients. IgG antibodies against herpesviruses, carotid intima-media thickness (cIMT), endothelial function through flow-mediated dilatation (FMD) of the brachial artery, and blood atherosclerosis biomarkers (hsCRP, TNF-a, IL-6, MCP-1, MDA, sCD14, sCD163, VCAM-1, ICAM-1, D-dimer, and PAI1) were measured. Results: 136 patients with HIV viral load ,200 copies/ml were included. 93.4% patients were infected with herpes simplex virus type-1, 55.9% with herpes simplex virus type-2, 97.1% with varicella-zoster virus, 65.4% with human herpesvirus-6, 91.2% with cytomegalovirus, and 99.3% with Epstein-Barr virus. Previous AIDS diagnosis was associated with higher cytomegalovirus IgG titers (23,000 vs 17,000 AU, P=0.011) and higher varicella-zoster virus IgG titers (3.19 vs 2.88 AU, P=0.047), and there was a positive correlation of the Framingham risk score with IgG levels against cytomegalovirus (Spearman’s Rho 0.216, P=0.016) and Herpes simplex virus-2 (Spearman’s Rho 0.293, P=0.001). IgG antibodies against cytomegalovirus correlated in adjusted analysis with the cIMT (P=0.030). High seropositivity for varicella-zoster virus (OR 2.91, 95% CI 1.05–8.01, P=0.039), and for cytomegalovirus (OR 3.79, 95% CI 1.20–11.97, P=0.023) were predictors for the highest quartile of the cIMT in adjusted analyses. PAI-1 levels were independently associated with cytomegalovirus IgG titers (P=0.041), IL-6 and ICAM-1 levels with varicella-zoster virus IgG (P=0.046 and P=0.035 respectively), and hsCRP levels with Herpes simplex virus-2 IgG (P=0.035). Conclusion: In virologically suppressed HIV-infected patients, antibody responses against herpesviruses are associated with subclinical atherosclerosis, and with increased inflammation and coagulation biomarkers.