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

TitleGBV-C viremia is associated with reduced CD4 expansion in HIV-infected people receiving HAART and interleukin-2 therapy.
Publication TypeJournal Article
Year of Publication2009
AuthorsStapleton JT, Chaloner K, Zhang J, Klinzman D, Souza IE, Xiang J, Landay A, Fahey J, Pollard R, Mitsuyasu R
JournalAIDS
Volume23
Issue5
Pagination605-10
Date Published2009 Mar 13
ISSN1473-5571
KeywordsAdolescent, Adult, Aged, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Female, Flaviviridae Infections, GB virus C, HIV Infections, HIV-1, Humans, Interleukin-2, Male, Middle Aged, Recombinant Proteins, Viremia
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.

DOI10.1097/QAD.0b013e32831f1b00
Alternate JournalAIDS
PubMed ID19194270
PubMed Central IDPMC2739595
Grant ListAI-27660 / AI / NIAID NIH HHS / United States
AI-58740 / AI / NIAID NIH HHS / United States
AI-69424 / AI / NIAID NIH HHS / United States
R01 AI058740 / AI / NIAID NIH HHS / United States
R01 AI058740-05 / AI / NIAID NIH HHS / United States
U01 AI069424 / AI / NIAID NIH HHS / United States
U01 AI069424-03 / AI / NIAID NIH HHS / United States