Impaired hepatitis C virus-specific T cell responses and recurrent hepatitis C virus in HIV coinfection
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Impaired hepatitis C virus-specific T cell responses and recurrent hepatitis C virus in HIV coinfection. / 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.
In: PLOS MED, Vol. 3, No. 12, 12.2006, p. e492.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Impaired hepatitis C virus-specific T cell responses and recurrent hepatitis C virus in HIV coinfection
AU - Kim, Arthur Y
AU - Schulze zur Wiesch, Julian
AU - Kuntzen, Thomas
AU - Timm, Joerg
AU - Kaufmann, Daniel E
AU - Duncan, Jared E
AU - Jones, Andrea M
AU - Wurcel, Alysse G
AU - Davis, Benjamin T
AU - Gandhi, Rajesh T
AU - Robbins, Gregory K
AU - Allen, Todd M
AU - Chung, Raymond T
AU - Lauer, Georg M
AU - Walker, Bruce D
PY - 2006/12
Y1 - 2006/12
N2 - 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.
AB - 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.
KW - CD4-Positive T-Lymphocytes/immunology
KW - Comorbidity
KW - Cross-Sectional Studies
KW - HIV Core Protein p24/immunology
KW - HIV-1/physiology
KW - Hepacivirus/genetics
KW - Hepatitis C/epidemiology
KW - Humans
KW - Immunoassay
KW - Interferon-gamma/immunology
KW - Lymphocyte Count
KW - RNA, Viral/analysis
KW - Recurrence
KW - Viremia/epidemiology
U2 - 10.1371/journal.pmed.0030492
DO - 10.1371/journal.pmed.0030492
M3 - SCORING: Journal article
C2 - 17194190
VL - 3
SP - e492
JO - PLOS MED
JF - PLOS MED
SN - 1549-1277
IS - 12
ER -