title: Cellular immune responses to HCV core increase and HCV RNA levels decrease during successful antiretroviral therapy.
abstract: BACKGROUND
  Hepatitis C virus (HCV) infection is a major cause of morbidity in HIV infected individuals. Coinfection with HIV is associated with diminished HCV-specific immune responses and higher HCV RNA levels.
  
  
  OBJECTIVE
  To investigate whether long-term combination antiretroviral therapy (cART) restores HCV-specific T cell responses and improves the control of HCV replication.
  
  
  METHODS
  T cell responses were evaluated longitudinally in 80 HIV/HCV coinfected individuals by ex vivo interferon-gamma-ELISpot responses to HCV core peptides, that predominantly stimulate CD4(+) T cells. HCV RNA levels were assessed by real-time PCR in 114 individuals.
  
  
  RESULTS
  The proportion of individuals with detectable T cell responses to HCV core peptides was 19% before starting cART, 24% in the first year on cART and increased significantly to 45% and 49% after 33 and 70 months on cART (p=0.001). HCV-specific immune responses increased in individuals with chronic (+31%) and spontaneously cleared HCV infection (+30%). Median HCV RNA levels before starting cART were 6.5 log(10) IU/ml. During long-term cART, median HCV-RNA levels slightly decreased compared to pre-cART levels (-0.3 log10 IU/ml, p=0.02).
  
  
  CONCLUSIONS
  Successful cART is associated with increasing cellular immune responses to HCV core peptides and with a slight long-term decrease in HCV RNA levels. These findings are in line with the favourable clinical effects of cART on the natural history of hepatitis C and with the current recommendation to start cART earlier in HCV/HIV coinfected individuals.
authors.affiliation: Klinik und Poliklinik für Infektiologie, University Hospital Berne and University of Berne, Inselspital PKT2B, 3010 Bern, Switzerland.
authors.forename: Janine
authors.initials: J
authors.lastname: Rohrbach
authors.forename: Nicola
authors.initials: N
authors.lastname: Robinson
authors.forename: Gillian
authors.initials: G
authors.lastname: Harcourt
authors.forename: Emma
authors.initials: E
authors.lastname: Hammond
authors.forename: Silvana
authors.initials: S
authors.lastname: Gaudieri
authors.forename: Meri
authors.initials: M
authors.lastname: Gorgievski
authors.forename: Amalio
authors.initials: A
authors.lastname: Telenti
authors.forename: Olivia
authors.initials: O
authors.lastname: Keiser
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hirschel
authors.forename: Matthias
authors.initials: M
authors.lastname: Hoffmann
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
authors.forename: Andri
authors.initials: A
authors.lastname: Rauch
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D018936:Hepatitis C Antigens / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007371:Interferon-gamma / Q000096:biosynthesis; D008137:Longitudinal Studies; D008297:Male; D012367:RNA, Viral / Q000097:blood; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014758:Viral Core Proteins / Q000276:immunology; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D018936:Hepatitis C Antigens; D012367:RNA, Viral; D014758:Viral Core Proteins; D007371:Interferon-gamma