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

• Published in: AIDS (London) Vol. 23; no. 5; pp. 605 - 610
• Main Authors: STAPLETON, Jack T, CHALONER, Kathryn, JINGYANG ZHANG, KLINZMAN, Donna, SOUZA, Inara E, JINHUA XIANG, LANDAY, Alan, FAHEY, John, POLLARD, Richard, MITSUYASU, Ronald
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 13-03-2009
• Subjects: Adolescent; Adult; Aged; AIDS/HIV; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral Therapy, Highly Active; Antiviral agents; Biological and medical sciences; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; Female; Flaviviridae Infections - complications; Flaviviridae Infections - immunology; Flavivirus; GB virus; GB virus C - isolation & purification; HIV Infections - complications; HIV Infections - drug therapy; HIV Infections - immunology; HIV-1 - isolation & purification; Human immunodeficiency virus; Human viral diseases; Humans; Infectious diseases; Interleukin-2 - therapeutic use; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Recombinant Proteins - therapeutic use; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral hepatitis; Viremia - complications; Viremia - immunology; interleukin-2; Viremia; Hepatic disease; Flavivirus; CD4 cell count; Interleukin 2; Immunological investigation; GBV-C; T-Lymphocyte; Antiviral; Viral hepatitis G; Hepatitis G virus; Immunopathology; Retroviridae; AIDS; GB virus C; Immune deficiency; Lentivirus; Infection; Virus; Numeration; Chemotherapy; Treatment; HIV; Viral disease; Digestive diseases; Human immunodeficiency virus; Flaviviridae
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/QAD.0b013e32831f1b00

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.
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.
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).
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.