title: CD4+ T-Cell-Dependent Reduction in Hepatitis C Virus-Specific Neutralizing Antibody Responses After Coinfection With Human Immunodeficiency Virus.
abstract: BACKGROUND
  Human immunodeficiency virus (HIV) infection leads to lower rates of hepatitis C virus (HCV) clearance after acute infection, higher HCV viremia, and accelerated progression of HCV-related fibrosis. The mechanisms underlying this acceleration of HCV progression by HIV are poorly understood, but HIV-induced dysfunction in the anti-HCV humoral immune response may play a role.
  
  
  METHODS
  To define the effect of HIV coinfection on the anti-HCV antibody response, we measured anti-HCV envelope binding antibody titers, neutralizing antibody (nAb) titers, and nAb breadth of serum from HCV-infected subjects isolated longitudinally before and after incident HIV infection.
  
  
  RESULTS
  A significant reduction in HCV envelope-specific binding antibody and nAb titers was detected in subjects with CD4(+) T-cell counts <350/mm(3) after HIV infection, and subjects with CD4(+) T-cell counts <200/mm(3) also showed a reduction in nAb breadth. Subjects who maintained CD4(+) T-cell counts ≥350/mm(3) displayed little to no decline in antibody levels.
  
  
  CONCLUSIONS
  Depletion of CD4(+) T cells by HIV infection results in a global decline in the anti-HCV envelope antibody response, including binding antibody titers, nAb titers, and nAb breadth.
authors.affiliation: Division of Infectious Diseases, Department of Medicine.
authors.forename: Justin R
authors.initials: JR
authors.lastname: Bailey
authors.affiliation: Viral Pathogenesis Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Dowd
authors.affiliation: Division of Infectious Diseases, Department of Medicine.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Snider
authors.affiliation: Division of Infectious Diseases, Department of Medicine.
authors.forename: William O
authors.initials: WO
authors.lastname: Osburn
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore.
authors.forename: Shruti H
authors.initials: SH
authors.lastname: Mehta
authors.affiliation: Division of Infectious Diseases, Department of Medicine Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Kirk
authors.affiliation: Division of Infectious Diseases, Department of Medicine.
authors.forename: David L
authors.initials: DL
authors.lastname: Thomas
authors.affiliation: Division of Infectious Diseases, Department of Medicine Department of Oncology, Johns Hopkins University School of Medicine.
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Ray
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D000918:Antibody Specificity; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000276:immunology; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000150:complications* / Q000276:immunology / Q000821:virology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000302:isolation & purification; D015819:Substance Abuse, Intravenous / Q000150:complications
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D012367:RNA, Viral
keywords: HCV; HIV; coinfection; neutralizing antibody