Jerome Kerzerho1, Elizabeth J McIlvaine, Patricia Anthony, Wendy J Mack, Chia-Hao Wang, Toni Frederick, Eva Operskalski, Zhi Chen, Lena Al-Harthi, Alan Landay, Mary A Young, Phyllis C Tien, Michael Augenbraun, Howard D Strickler, Omid Akbari, Elizabeth T Golub, Gerald B Sharp, Andrea Kovacs. 1. Departments of *Molecular Microbiology and Immunology;†Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA;‡Maternal, Child, and Adolescent Center for Infectious Diseases and Virology, University of Southern California, Keck School of Medicine, Los Angeles, CA;§Department of Immunology, Microbiology, Rush University Medical Center, Chicago, IL;‖Division of Infectious Diseases, Georgetown University, Washington, DC;¶Department of Medicine, University of California, San Francisco, and San Francisco Veterans Affair Medical Center, San Francisco, CA;#Department of Medicine, SUNY Downstate College of Medicine, Brooklyn, NY;**Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY;††Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; and‡‡Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda MD.
Abstract
OBJECTIVES: Hepatitis C virus (HCV) infection causes an alteration in T-cell maturation and activation in patients coinfected with human immunodeficiency virus (HIV). Because interleukin 7 (IL-7) is a major cytokine controlling T-cell homeostasis, we analyzed the potential influence of HCV coinfection on circulating IL-7 levels in HIV-infected women before and after highly active antiretroviral therapy (HAART). DESIGN AND METHODS: This prospective study included 56 HIV monoinfected, 55 HIV/HCV coinfected without HCV viremia, 132 HIV/HCV coinfected with HCV viremia, and 61 HIV/HCV-uninfected women for whom plasma levels of IL-7 were determined by enzyme-linked immunosorbent assay at 1 or more follow-up visits before and after HAART. Cross-sectional analyses of the associations between plasma IL-7 levels and HCV infection, demographic, clinical, and immunologic characteristics were evaluated using univariate and multivariate linear regression models before and after HAART. RESULTS: In multivariate models, IL-7 levels were significantly higher in coinfected HCV viremic women than in HIV monoinfected women (multiplicative effect = 1.48; 95% confidence interval: 1.01 to 2.16; P = 0.04) before HAART, but were similar between these two groups among women after HAART. In addition to HCV viremia, higher IL-7 levels were associated with older age (P = 0.02), lower CD4(+) T-cell count (P = 0.0007), and higher natural killer T-cell count (P = 0.02) in women before HAART. Among HAART-treated women, only lower CD4(+) T-cell count was significantly associated with IL-7 level (P = 0.006). CONCLUSIONS: Our data demonstrate that in HIV-infected women, circulating levels of IL-7 are strongly associated with CD4 T-cell depletion both before and after HAART. Our data also demonstrate that HCV viremia increases circulating IL-7 levels before HAART but not after HAART in coinfected women. This suggests that the effect of HCV on lymphopenia is abrogated by HAART.
OBJECTIVES:Hepatitis C virus (HCV) infection causes an alteration in T-cell maturation and activation in patients coinfected with human immunodeficiency virus (HIV). Because interleukin 7 (IL-7) is a major cytokine controlling T-cell homeostasis, we analyzed the potential influence of HCV coinfection on circulating IL-7 levels in HIV-infectedwomen before and after highly active antiretroviral therapy (HAART). DESIGN AND METHODS: This prospective study included 56 HIV monoinfected, 55 HIV/HCV coinfected without HCV viremia, 132 HIV/HCV coinfected with HCV viremia, and 61 HIV/HCV-uninfected women for whom plasma levels of IL-7 were determined by enzyme-linked immunosorbent assay at 1 or more follow-up visits before and after HAART. Cross-sectional analyses of the associations between plasma IL-7 levels and HCV infection, demographic, clinical, and immunologic characteristics were evaluated using univariate and multivariate linear regression models before and after HAART. RESULTS: In multivariate models, IL-7 levels were significantly higher in coinfected HCV viremicwomen than in HIV monoinfected women (multiplicative effect = 1.48; 95% confidence interval: 1.01 to 2.16; P = 0.04) before HAART, but were similar between these two groups among women after HAART. In addition to HCV viremia, higher IL-7 levels were associated with older age (P = 0.02), lower CD4(+) T-cell count (P = 0.0007), and higher natural killer T-cell count (P = 0.02) in women before HAART. Among HAART-treated women, only lower CD4(+) T-cell count was significantly associated with IL-7 level (P = 0.006). CONCLUSIONS: Our data demonstrate that in HIV-infectedwomen, circulating levels of IL-7 are strongly associated with CD4 T-cell depletion both before and after HAART. Our data also demonstrate that HCV viremia increases circulating IL-7 levels before HAART but not after HAART in coinfected women. This suggests that the effect of HCV on lymphopenia is abrogated by HAART.
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