Herpesvirus and GB Virus C Infections in Men With and Without HIV-1 Who Have Sex with Men

Abstract

In men with (MWH) and without (MWOH) HIV-1 infection, we longitudinally evaluated the prevalence of human herpesvirus (HHV) and GB virus C (GBV-C) infections and examined associations with plasma HIV-1 load and inflammatory markers. We analyzed 11,874 plasma samples (collected from 1984 to 2009) from 1,882 men who have sex with men in the Multicenter AIDS Cohort Study to quantify four HHVs [cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 8 (HHV-8), and human herpesvirus 6 (HHV-6)] and GBV-C. HHV and GBV-C viral loads were measured using quantitative Polymerase Chain Reaction (PCR) and Reverse Transcription (RT)-PCR, respectively. Differences in viral prevalence and concentrations were assessed using multivariable logistic and linear regression. Associations between HHV viremia and 24 inflammatory and immune activation biomarkers were evaluated using generalized gamma models. Age-related biomarker trajectories were analyzed using linear mixed models among MWH with sustained suppression due to HIV-1 antiretroviral therapy. MWH with detectable plasma HIV-1 RNA had significantly higher odds of CMV, EBV, and HHV-8 viremia compared with those with undetectable plasma HIV-1 RNA, who in turn had higher odds than MWOH. CMV and EBV viremia were associated with higher levels of multiple inflammatory markers. Among MWH with consistent viral suppression, no significant differences were observed in age-related biomarker trajectories. Overall, active HHV infection, as indicated by viremia, was associated with significantly higher plasma HIV-1 loads and increased inflammatory marker levels—particularly in the presence of detectable plasma HIV-1 RNA. Our study supports the hypothesis that active HHV infections may exacerbate HIV-1 disease progression in MWH.