Impaired hepatitis C virus-specific T cell responses and recurrent hepatitis C virus in HIV coinfection
Schulze zur Wiesch, Julian
Duncan, Jared E.
Jones, Andrea M.
Wurcel, Alysse G.
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CitationKim, Arthur Y., Julian Schulze zur Wiesch, Thomas Kuntzen, Joerg Timm, Daniel E Kaufmann, Jared E Duncan, Andrea M Jones, Alysse G. Wurcel, Benjamin T. Davis, Rajesh T. Gandhi, Gregory K. Robbins, Todd M. Allen, Raymond T. Chung, Georg M. Lauer, and Bruce D. Walker. 2006. Impaired hepatitis C virus-specific T cell responses and recurrent hepatitis C virus in HIV coinfection. PLoS Medicine 3(12): e492.
AbstractBackground: 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.
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