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

• Published in: PLoS medicine 2006-12, Vol.3 (12), p.e492-e492
• Main Authors: Kim, Arthur Y, Schulze zur Wiesch, Julian, Kuntzen, Thomas, Timm, Joerg, Kaufmann, Daniel E, Duncan, Jared E, Jones, Andrea M, Wurcel, Alysse G, Davis, Benjamin T, Gandhi, Rajesh T, Robbins, Gregory K, Allen, Todd M, Chung, Raymond T, Lauer, Georg M, Walker, Bruce D
• Format: Article
• Language: English
• Subjects: Analysis; CD4-Positive T-Lymphocytes - immunology; Charitable foundations; Comorbidity; Cross-Sectional Studies; Health aspects; Hepacivirus - genetics; Hepacivirus - immunology; Hepatitis C; Hepatitis C - epidemiology; Hepatitis C - immunology; Hepatitis C virus; HIV; HIV Core Protein p24 - immunology; HIV Infection/AIDS; HIV-1 - physiology; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Immunoassay; Immunology; Infections; Infectious Diseases; Interferon; Interferon-gamma - immunology; Liver diseases; Lymphocyte Count; Lymphocytes; Microbiology; Recurrence; RNA, Viral - analysis; Sexually transmitted diseases; Sexually transmitted infections - other than HIV/AIDS; T cells; Viremia - epidemiology; Viremia - immunology; Virology
• ISSN: 1549-1676; 1549-1277; 1549-1676
• DOI: 10.1371/journal.pmed.0030492

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. 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). 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.