Contribution of human herpesvirus 8 and herpes simplex type 2 to progression of carotid intima-media thickness in people living with HIV

Abstract

Background. Human herpesvirus 8 (HHV-8) is a lymphotropic and vasculotropic herpesvirus with potential pro-atherogenic effects. We explored the influence of coinfection with HHV-8 and other herpesviruses on the rate of progression of carotid intima-media thickness (cIMT) in virologically suppressed people living with HIV (PLWH). Methods. Prospective cohort study including men who have sex with men (MSM) infected with HIV. At the baseline visit, IgG antibodies against HHV-8 and other herpesviruses, highly sensitive C-reactive protein (hsCRP) levels, and Framingham risk scores were measured. To evaluate the progression of cIMT, successive measurements with high-resolution carotid artery ultrasound were performed over an 8-year period. Adjusted general linear mixed models were used to assess factors associated with faster cIMT progression. Results. One hundred forty-one participants with suppressed HIV-RNA (<200 copies/mL) at cIMT measurement during the study period were included. Forty-six (31.3%) were coinfected with HHV-8 and 76 (54%) with herpes simplex virus 2 (HSV-2). Factors associated with faster cIMT progression adjusting for CD4 cell counts, time between cIMT measurements, hepatitis C, varicella zoster virus, and cytomegalovirus coinfection were seropositivity for HHV-8 (P = .059), HSV-2+HHV-8 coinfection (P = .027), Framingham risk score (P = .057), and hsCRP (P = .027). Coinfection with HHV-8 was independently associated with higher levels of hsCRP (odds ratio, 1.09; 95% confidence interval, 1.02 to 1.17; P = .016). When hsCRP and HHV-8 were simultaneously included in the adjusted model, the relationship of HHV-8 with cIMT progression was attenuated. Conclusions. HHV-8 might contribute to progression of cIMT with a more prominent role when it coinfects with HHV-2 in virologically suppressed PLWH, and this effect could be driven by systemic inflammation.