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

Jack T. Stapleton, Kathryn Chaloner, Jingyang Zhang, Donna Klinzman, Inara E. Souza, Jinhua Xiang, Alan Landay, John Fahey, Richard B Pollard, Ronald Mitsuyasu

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28 Scopus citations

Abstract

Objective: lnterleukin-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-1α, MIP-1 β, 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/μl 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/μl). 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.

Original languageEnglish (US)
Pages (from-to)605-610
Number of pages6
JournalAIDS
Volume23
Issue number5
DOIs
StatePublished - Mar 13 2009

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Keywords

  • CD4 cell count
  • GB virus C
  • GBV-C
  • HIV
  • Interleukin-2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Stapleton, J. T., Chaloner, K., Zhang, J., Klinzman, D., Souza, I. E., Xiang, J., Landay, A., Fahey, J., Pollard, R. B., & Mitsuyasu, R. (2009). GBV-C viremia is associated with reduced CD4 expansion in HIV-infected people receiving HAART and interleukin-2 therapy. AIDS, 23(5), 605-610. https://doi.org/10.1097/QAD.0b013e32831f1b00