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


RESULTS
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.
Kim
Arthur Y
AY
Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America. akim1@partners.org
Schulze zur Wiesch
Julian
J
Kuntzen
Thomas
T
Timm
Joerg
J
Kaufmann
Daniel E
DE
Duncan
Jared E
JE
Jones
Andrea M
AM
Wurcel
Alysse G
AG
Davis
Benjamin T
BT
Gandhi
Rajesh T
RT
Robbins
Gregory K
GK
Allen
Todd M
TM
Chung
Raymond T
RT
Lauer
Georg M
GM
Walker
Bruce D
BD
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015897:Comorbidity; D003430:Cross-Sectional Studies; D016655:HIV Core Protein p24 / Q000276:immunology; D015497:HIV-1 / Q000502:physiology*; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000453:epidemiology* / Q000276:immunology; D006801:Humans; D007118:Immunoassay; D007371:Interferon-gamma / Q000276:immunology; D018655:Lymphocyte Count; D012367:RNA, Viral / Q000032:analysis; D012008:Recurrence; D014766:Viremia / Q000453:epidemiology* / Q000276:immunology
D016655:HIV Core Protein p24; D012367:RNA, Viral; D007371:Interferon-gamma