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Asymptomatic CMV Replication during Early HIV-infection is Associated with Lower CD4/CD8 Ratio during HIV Treatment

  1. Sara Gianella1
  1. 1University of California, San Diego, La Jolla, CA, USA
  2. 2Veterans Affairs San Diego Healthcare System, San Diego, CA, USA
  3. 3Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, OH USA
  1. Corresponding author: Sara Gianella, University of California San Diego, 9500 Gilman Drive MC 0679, La Jolla, CA 92093-0679, USA, Tel: 858-642-1620; Fax: (858) 552-7445, E-mail: gianella{at}ucsd.edu

Abstract

Background. A low CD4/CD8 ratio in 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 CMV and 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 (PBMC) 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 (EDI), and were followed for a median of 29.1 months thereafter. Levels of CMV and EBV DNA were measured at each time-point. 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 a higher levels of CD8+ T-cell counts (p<0.05), without affecting CD4+ T-cell counts (p>0.1). Age was negatively associated with the 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.

UNCORRECTED PROOF

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