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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. 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.

journal_name

PLoS Med

journal_title

PLoS medicine

authors

Kim AY,Schulze zur Wiesch J,Kuntzen T,Timm J,Kaufmann DE,Duncan JE,Jones AM,Wurcel AG,Davis BT,Gandhi RT,Robbins GK,Allen TM,Chung RT,Lauer GM,Walker BD

doi

10.1371/journal.pmed.0030492

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

e492

issue

eissn

1549-1277

issn

1549-1676

pii

06-PLME-RA-0235R2

journal_volume

pub_type

杂志文章,多中心研究

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