GBV-C viremia is associated with reduced CD4 expansion in HIV-infected people receiving HAART and interleukin-2 therapy.

Abstract

OBJECTIVE:

Interleukin-2 (IL-2) is a cytokine with multiple effects on lymphocytes including induction of CD4 T-cell proliferation. IL-2 administration has been shown to increase CD4 cell counts in HIV-infected people receiving antiretroviral therapy. GB virus C (GBV-C) is an apparently nonpathogenic flavivirus that replicates in CD4 T cells and inhibits HIV replication in vitro by mechanisms including downregulation of HIV entry coreceptors (CCR5 and CXCR4) and induction of chemokines (RANTES, MIP-1alpha, MIP-1 beta, and SDF-1). GBV-C replication is significantly inhibited in vitro by activation of primary CD4 cell cultures with IL-2 and phytohemagglutinin. We sought to determine if there is an interaction between GBV-C and IL-2 in vivo.

METHODS:

GBV-C viremia status was characterized in 92 HIV-infected individuals participating in a randomized trial of IL-2 and antiretroviral therapy [AIDS Clinical Trials Group Study (ACTG) 328]. Changes in CD4 cell counts and HIV RNA levels in individuals assigned IL-2 were compared with those in individuals assigned antiretroviral therapy alone.

RESULTS:

Individuals lacking GBV-C viremia had a significantly greater rise in CD4 cell count with IL-2, compared with GBV-C viremic individuals (by 511 cells/microl at week 84; interaction P = 0.02): GBV-C viremic individuals assigned IL-2 did not demonstrate a significant increase in CD4 cell count compared with individuals not assigned to receive IL-2 (95% CI for difference -255 to 397 cells/microl).

CONCLUSION:

GBV-C viremia was associated with a block in CD4 cell expansion following IL-2 therapy in the ACTG 328 study, and GBV-C status may be an important factor in IL-2 treatment response.

• Authors: Jack T Stapleton, Kathryn Chaloner, Jingyang Zhang, Donna Klinzman, Inara E Souza, Jinhua Xiang, Alan Landay, John Fahey, Richard Pollard, Ronald Mitsuyasu
• Journal: AIDS (London, England) (AIDS) Vol. 23 Issue 5 Pg. 605-10 (Mar 13 2009) ISSN: 1473-5571 [Electronic] England
• PMID: 19194270 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Anti-HIV Agents
• Interleukin-2
• Recombinant Proteins

Topics

• Adolescent
• Adult
• Aged
• Anti-HIV Agents (therapeutic use)
• Antiretroviral Therapy, Highly Active
• CD4 Lymphocyte Count
• CD4-Positive T-Lymphocytes (drug effects, immunology)
• Female
• Flaviviridae Infections (complications, immunology)
• GB virus C (isolation & purification)
• HIV Infections (complications, drug therapy, immunology)
• HIV-1 (isolation & purification)
• Humans
• Interleukin-2 (therapeutic use)
• Male
• Middle Aged
• Recombinant Proteins (therapeutic use)
• Viremia (complications, immunology)