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

Research output: Contribution to journalArticle

28 Citations (Scopus)

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

Fingerprint

GB virus C
Viremia
Highly Active Antiretroviral Therapy
Interleukin-2
HIV
CD4 Lymphocyte Count
Therapeutics
Acquired Immunodeficiency Syndrome
Clinical Trials
T-Lymphocytes
Flavivirus
Chemokine CCL5
Primary Cell Culture
Phytohemagglutinins
Virus Replication
Chemokines
Down-Regulation

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., ... 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

GBV-C viremia is associated with reduced CD4 expansion in HIV-infected people receiving HAART and interleukin-2 therapy. / Stapleton, Jack T.; Chaloner, Kathryn; Zhang, Jingyang; Klinzman, Donna; Souza, Inara E.; Xiang, Jinhua; Landay, Alan; Fahey, John; Pollard, Richard B; Mitsuyasu, Ronald.

In: AIDS, Vol. 23, No. 5, 13.03.2009, p. 605-610.

Research output: Contribution to journalArticle

Stapleton, JT, Chaloner, K, Zhang, J, Klinzman, D, Souza, IE, Xiang, J, Landay, A, Fahey, J, Pollard, RB & Mitsuyasu, R 2009, 'GBV-C viremia is associated with reduced CD4 expansion in HIV-infected people receiving HAART and interleukin-2 therapy', AIDS, vol. 23, no. 5, pp. 605-610. https://doi.org/10.1097/QAD.0b013e32831f1b00
Stapleton, Jack T. ; Chaloner, Kathryn ; Zhang, Jingyang ; Klinzman, Donna ; Souza, Inara E. ; Xiang, Jinhua ; Landay, Alan ; Fahey, John ; Pollard, Richard B ; Mitsuyasu, Ronald. / GBV-C viremia is associated with reduced CD4 expansion in HIV-infected people receiving HAART and interleukin-2 therapy. In: AIDS. 2009 ; Vol. 23, No. 5. pp. 605-610.
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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.",
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AU - Chaloner, Kathryn

AU - Zhang, Jingyang

AU - Klinzman, Donna

AU - Souza, Inara E.

AU - Xiang, Jinhua

AU - Landay, Alan

AU - Fahey, John

AU - Pollard, Richard B

AU - Mitsuyasu, Ronald

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N2 - 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.

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KW - HIV

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