title: A Comprehensive Analysis of the Impact of HIV on HCV Immune Responses and Its Association with Liver Disease Progression in a Unique Plasma Donor Cohort.
abstract: OBJECTIVE
  Human Immunodeficiency Virus (HIV) and Hepatitis C virus (HCV) co-infection is recognized as a major cause of morbidity and mortality among HIV-1 infected patients. Our understanding of the impact of HIV infection on HCV specific immune responses and liver disease outcome is limited by the heterogeneous study populations with genetically diverse infecting viruses, varying duration of infection and anti-viral treatment.
  
  
  METHODS
  Viral-specific immune responses in a cohort of 151 HCV mono- and HIV co-infected former plasma donors infected with a narrow source of virus were studied. HCV and HIV specific T cell responses were correlated with clinical data.
  
  
  RESULTS
  HIV-1 accelerated liver disease progression and decreased HCV specific T cell immunity. The magnitude of HCV specific T cell responses inversely correlated with lower HCV RNA load and reduced liver injury as assessed by non-invasive markers of liver fibrosis. HIV co-infection reduced the frequency of HCV specific CD4+ T cells with no detectable effect on CD8+ T cells or neutralizing antibody levels.
  
  
  CONCLUSIONS
  Our study highlights the impact of HIV co-infection on HCV specific CD4+ T cell responses in a unique cohort of patients for both HCV and HIV and suggests a crucial role for these cells in controlling chronic HCV replication and liver disease progression.
authors.affiliation: You'an-Oxford Centre for Clinical Research, Beijing You'an Hospital, Capital Medical University, Beijing, China.|CAMS- Oxford University joint International Centre for Translational Immunology, Nuffield and Radcliffe departments of Medicine, University of Oxford, Oxford, United Kingdom.|Beijing Key Laboratory for Biomarkers in Infection Related Diseases (BZ0373), Beijing, China.
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Zhang
authors.affiliation: You'an-Oxford Centre for Clinical Research, Beijing You'an Hospital, Capital Medical University, Beijing, China.|CAMS- Oxford University joint International Centre for Translational Immunology, Nuffield and Radcliffe departments of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.|Department of Microbiology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.
authors.forename: Ushani S
authors.initials: US
authors.lastname: Rajapaksa
authors.affiliation: Viral Hepatitis Laboratory, Centre for Human Virology, College of Medical and Dental Sciences, University of Birmingham, United Kingdom.
authors.forename: Tessa M
authors.initials: TM
authors.lastname: Lawrence
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Yan-Chun
authors.initials: YC
authors.lastname: Peng
authors.affiliation: You'an-Oxford Centre for Clinical Research, Beijing You'an Hospital, Capital Medical University, Beijing, China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Liu
authors.affiliation: Beijing Di'Tan Hospital, Capital Medical University, Beijing, China.
authors.forename: Keyi
authors.initials: K
authors.lastname: Xu
authors.affiliation: Viral Hepatitis Laboratory, Centre for Human Virology, College of Medical and Dental Sciences, University of Birmingham, United Kingdom.
authors.forename: Ke
authors.initials: K
authors.lastname: Hu
authors.affiliation: You'an-Oxford Centre for Clinical Research, Beijing You'an Hospital, Capital Medical University, Beijing, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
authors.affiliation: You'an-Oxford Centre for Clinical Research, Beijing You'an Hospital, Capital Medical University, Beijing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.affiliation: You'an-Oxford Centre for Clinical Research, Beijing You'an Hospital, Capital Medical University, Beijing, China.
authors.forename: Huanqin
authors.initials: H
authors.lastname: Sun
authors.affiliation: You'an-Oxford Centre for Clinical Research, Beijing You'an Hospital, Capital Medical University, Beijing, China.
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Yan
authors.affiliation: Computational Biology Research Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Emmanouela
authors.initials: E
authors.lastname: Repapi
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Rowland-Jones
authors.affiliation: University Hospital Freiburg, Department of Medicine II, Hugstetter Str 55, 79106, Freiburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Thimme
authors.affiliation: Viral Hepatitis Laboratory, Centre for Human Virology, College of Medical and Dental Sciences, University of Birmingham, United Kingdom.
authors.forename: Jane A
authors.initials: JA
authors.lastname: McKeating
authors.affiliation: You'an-Oxford Centre for Clinical Research, Beijing You'an Hospital, Capital Medical University, Beijing, China.|CAMS- Oxford University joint International Centre for Translational Immunology, Nuffield and Radcliffe departments of Medicine, University of Oxford, Oxford, United Kingdom.|MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Tao
authors.initials: T
authors.lastname: Dong
mesh_terms: D000328:Adult; D000368:Aged; D057134:Antibodies, Neutralizing / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers; D001782:Blood Donors; D002681:China / Q000453:epidemiology; D060085:Coinfection; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000453:epidemiology* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000150:complications / Q000453:epidemiology* / Q000276:immunology* / Q000821:virology; D018937:Hepatitis C Antibodies / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008103:Liver Cirrhosis / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D019562:Viral Load; D014779:Virus Replication
chemical_list: D057134:Antibodies, Neutralizing; D015415:Biomarkers; D018937:Hepatitis C Antibodies; D007371:Interferon-gamma