Impaired hepatitis C virus-specific T cell responses and recurrent hepatitis C virus in HIV coinfection

PLoS Med. 2006 Dec;3(12):e492. doi: 10.1371/journal.pmed.0030492.


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.

Methods and findings: 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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology
  • Comorbidity
  • Cross-Sectional Studies
  • HIV Core Protein p24 / immunology
  • HIV-1 / physiology*
  • Hepacivirus / genetics
  • Hepacivirus / immunology*
  • Hepatitis C / epidemiology*
  • Hepatitis C / immunology
  • Humans
  • Immunoassay
  • Interferon-gamma / immunology
  • Lymphocyte Count
  • RNA, Viral / analysis
  • Recurrence
  • Viremia / epidemiology*
  • Viremia / immunology


  • HIV Core Protein p24
  • RNA, Viral
  • Interferon-gamma