Background . A low CD4/CD8 ratio in human immunodeficiency virus (HIV)–infected individuals is associated with inflammation and higher risk of non-AIDS morbidity and mortality. In this study, we investigated the effect of subclinical cytomegalovirus (CMV) and Epstein-Barr virus (EBV) replication on CD4+ and CD8+ T-cell dynamics when antiretroviral therapy (ART) is started during early infection.

Methods . We investigated 604 peripheral blood mononuclear cell samples from 108 CMV- and EBV-seropositive HIV-infected men who have sex with men, who started ART within a median of 4 months from their estimated date of infection and were followed for a median of 29.1 months thereafter. Levels of CMV and EBV DNA were measured at each timepoint. Mixed-effects asymptotic regression models were applied to characterize CD4+ and CD8+ T-cell dynamics, and Bayesian hierarchical models were used to quantify individual differences in CMV and EBV DNA replication.

Results . Higher levels of subclinical CMV replication were associated with lower predicted maximum levels of CD4/CD8 ratio (p < 0.05), which was driven by higher levels of CD8+ T-cell counts (p < 0.05), without affecting CD4+ T-cell counts (p > 0.1). Age was negatively associated with CD4/CD8 levels (p < 0.05), and this effect was independent of the CMV association (p < 0.05 for both CMV and age in a multivariate model).

Conclusions . Subclinical CMV replication in blood cells during early HIV infection and younger age were associated with lower CD4/CD8 ratios during suppressive ART. These findings suggest that active CMV infection in the setting of treated HIV may represent an attractive potential target for therapeutic intervention.