| Publication Abstract Display | | Type: Published Manuscript | | Title: Asymptomatic CMV replication during early HIV-infection is associated with lower CD4/CD8 ratio during HIV treatment. | | Authors: Smith DM, Nakazawa M, Freeman ML, Anderson CM, Oliveira MF, Little SJ, Gianella S | | Year: 2016 | | Publication: Clinical Infectious Diseases : An Official Publication of The Infectious Diseases Society of America | | Volume: 63 Issue: 11 Pages: 1517-1524 | | Abstract: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 < .05), which was driven by higher levels of CD8+ T-cell counts (P < .05), without affecting CD4+ T-cell counts (P > .1). Age was negatively associated with CD4/CD8 levels (P < .05), and this effect was independent of the CMV association (P < .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. |
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