title: Impact of Hepatitis C Virus on the Circulating Levels of IL-7 in HIV-1 Coinfected Women.
abstract: OBJECTIVE
  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).
  
  
  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.
authors.affiliation: 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.
authors.forename: Jerome
authors.initials: J
authors.lastname: Kerzerho
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: McIlvaine
authors.forename: Patricia
authors.initials: P
authors.lastname: Anthony
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Mack
authors.forename: Chia-Hao
authors.initials: CH
authors.lastname: Wang
authors.forename: Toni
authors.initials: T
authors.lastname: Frederick
authors.forename: Eva
authors.initials: E
authors.lastname: Operskalski
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
authors.forename: Lena
authors.initials: L
authors.lastname: Al-Harthi
authors.forename: Alan
authors.initials: A
authors.lastname: Landay
authors.forename: Mary A
authors.initials: MA
authors.lastname: Young
authors.forename: Phyllis C
authors.initials: PC
authors.lastname: Tien
authors.forename: Michael
authors.initials: M
authors.lastname: Augenbraun
authors.forename: Howard D
authors.initials: HD
authors.lastname: Strickler
authors.forename: Omid
authors.initials: O
authors.lastname: Akbari
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Golub
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Sharp
authors.forename: Andrea
authors.initials: A
authors.lastname: Kovacs
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D060085:Coinfection; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000150:complications / Q000276:immunology*; D006801:Humans; D015851:Interleukin-7 / Q000097:blood*; D008875:Middle Aged; D055611:Natural Killer T-Cells; D011446:Prospective Studies; D014766:Viremia
chemical_list: C508605:IL7 protein, human; D015851:Interleukin-7