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Clin Infect Dis. 2016 Dec 1;63(11):1517-1524. Epub 2016 Sep 6.

Asymptomatic CMV Replication During Early Human Immunodeficiency Virus (HIV) Infection Is Associated With Lower CD4/CD8 Ratio During HIV Treatment.

Author information

1
University of California, San Diego, La Jolla.
2
Veterans Affairs San Diego Healthcare System, San Diego, California.
3
Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio.

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.

KEYWORDS:

ART; CD4/CD8 ratio; Epstein-Barr virus; HIV; cytomegalovirus

PMID:
27601222
PMCID:
PMC5106612
DOI:
10.1093/cid/ciw612
[Indexed for MEDLINE]
Free PMC Article

MeSH terms, Substance, Grant support

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