title: Association of chronic hepatitis C infection with T-cell phenotypes in HIV-negative and HIV-positive women.
abstract: BACKGROUND
  Hepatitis C virus (HCV) viremia is thought to have broad systemic effects on the cellular immune system that go beyond its impact on just those T cells that are HCV specific. However, previous studies of chronic HCV and circulating T-cell subsets (activation and differentiation phenotypes) in HIV negatives used general population controls, rather than a risk-appropriate comparison group. Studies in HIV positives did not address overall immune status (total CD4⁺ count).
  
  
  METHODS
  We used fresh blood from HIV-positive and at-risk HIV-negative women, with and without chronic HCV, to measure percentages of activated CD4⁺ and CD8⁺ T cells, Tregs, and T-cell differentiation phenotypes (naive, central memory, effector memory (EM), and terminally differentiated effector). This included 158 HIV negatives and 464 HIV positives, of whom 18 and 63, respectively, were HCV viremic.
  
  
  RESULTS
  In multivariate models of HIV negatives, HCV viremia was associated with 25% fewer naive CD4⁺ (P = 0.03), 33% more EM CD4⁺ (P = 0.0002), and 37% fewer central memory CD8⁺ (P = 0.02) T cells. Among HIV positives, we observed only 1 of these 3 relationships: higher percentage of EM CD4⁺ among HCV viremic women. Furthermore, the association with EM CD4⁺ among HIV positives was limited to individuals with diminished immune status (total CD4⁺ count ≤500 cells/μL), as were associations of HCV viremia with higher percentages of activated CD4⁺ and Tregs. Among HIV positives with high CD4⁺ count, no significant associations were observed.
  
  
  CONCLUSIONS
  These data suggest that HCV viremia in HIV negatives is associated with accelerated T-cell differentiation, but among HIV positives, the impact of HCV viremia is less straightforward and varies by total CD4v count.
authors.affiliation: *Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY; †Department of Medicine, Montefiore Medical Center, Bronx, NY; ‡Department of Pediatrics, University of Southern California, Los Angeles, CA; §Department of Medicine, University of California San Francisco, San Francisco, CA; ‖Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; ¶Department of Medicine, CORE Center/Stroger Hospital of Cook County, Chicago, IL; #Department of Medicine, Georgetown University Medical Center, Washington, DC; **Department of Medicine, State University of New York Downstate Medical Center, Brooklyn, NY; ††Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL; and ‡‡Division of Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of Science, Utrecht University, the Netherlands.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kuniholm
authors.forename: Xianhong
authors.initials: X
authors.lastname: Xie
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kaplan
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Xue
authors.forename: Andrea
authors.initials: A
authors.lastname: Kovacs
authors.forename: Marion G
authors.initials: MG
authors.lastname: Peters
authors.forename: Eric C
authors.initials: EC
authors.lastname: Seaberg
authors.forename: Audrey L
authors.initials: AL
authors.lastname: French
authors.forename: Mary A
authors.initials: MA
authors.lastname: Young
authors.forename: Michael
authors.initials: M
authors.lastname: Augenbraun
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Martinson
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Bush
authors.forename: Alan L
authors.initials: AL
authors.lastname: Landay
authors.forename: Howard D
authors.initials: HD
authors.lastname: Strickler
mesh_terms: D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D018023:HIV Seronegativity / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008875:Middle Aged; D015999:Multivariate Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D019562:Viral Load; D055815:Young Adult