title: Impaired hepatitis C virus-specific T cell responses and recurrent hepatitis C virus in HIV coinfection.
abstract: BACKGROUND
  Hepatitis C virus (HCV)-specific T cell responses are critical for spontaneous resolution of HCV viremia. Here we examined the effect of a lymphotropic virus, HIV-1, on the ability of coinfected patients to maintain spontaneous control of HCV infection.
  
  
  RESULTS
  We measured T cell responsiveness by lymphoproliferation and interferon-gamma ELISPOT in a large cohort of HCV-infected individuals with and without HIV infection. Among 47 HCV/HIV-1-coinfected individuals, spontaneous control of HCV was associated with more frequent HCV-specific lymphoproliferative (LP) responses (35%) compared to coinfected persons who exhibited chronic HCV viremia (7%, p = 0.016), but less frequent compared to HCV controllers who were not HIV infected (86%, p = 0.003). Preservation of HCV-specific LP responses in coinfected individuals was associated with a higher nadir CD4 count (r(2) = 0.45, p < 0.001) and the presence and magnitude of the HCV-specific CD8(+) T cell interferon-gamma response (p = 0.0014). During long-term follow-up, recurrence of HCV viremia occurred in six of 25 coinfected individuals with prior control of HCV, but in 0 of 16 HIV-1-negative HCV controllers (p = 0.03, log rank test). In these six individuals with recurrent HCV viremia, the magnitude of HCV viremia following recurrence inversely correlated with the CD4 count at time of breakthrough (r = -0.94, p = 0.017).
  
  
  CONCLUSIONS
  These results indicate that HIV infection impairs the immune response to HCV-including in persons who have cleared HCV infection-and that HIV-1-infected individuals with spontaneous control of HCV remain at significant risk for a second episode of HCV viremia. These findings highlight the need for repeat viral RNA testing of apparent controllers of HCV infection in the setting of HIV-1 coinfection and provide a possible explanation for the higher rate of HCV persistence observed in this population.
authors.affiliation: Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America. akim1@partners.org
authors.forename: Arthur Y
authors.initials: AY
authors.lastname: Kim
authors.forename: Julian
authors.initials: J
authors.lastname: Schulze zur Wiesch
authors.forename: Thomas
authors.initials: T
authors.lastname: Kuntzen
authors.forename: Joerg
authors.initials: J
authors.lastname: Timm
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Kaufmann
authors.forename: Jared E
authors.initials: JE
authors.lastname: Duncan
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Jones
authors.forename: Alysse G
authors.initials: AG
authors.lastname: Wurcel
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Davis
authors.forename: Rajesh T
authors.initials: RT
authors.lastname: Gandhi
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Robbins
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Chung
authors.forename: Georg M
authors.initials: GM
authors.lastname: Lauer
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015897:Comorbidity; D003430:Cross-Sectional Studies; D016655:HIV Core Protein p24 / Q000276:immunology; D015497:HIV-1 / Q000502:physiology*; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000453:epidemiology* / Q000276:immunology; D006801:Humans; D007118:Immunoassay; D007371:Interferon-gamma / Q000276:immunology; D018655:Lymphocyte Count; D012367:RNA, Viral / Q000032:analysis; D012008:Recurrence; D014766:Viremia / Q000453:epidemiology* / Q000276:immunology
chemical_list: D016655:HIV Core Protein p24; D012367:RNA, Viral; D007371:Interferon-gamma