Transient liver injury associated with the early recovery of HCV-specific T-cell responses and HCV rebound in HIV-1/HCV coinfected patients undergoing highly active antiretroviral therapy.
OBJECTIVE
HIV-1/hepatitis C virus (HCV) coinfection accelerates the progression of liver disease to cirrhosis, particularly in individuals with low CD4 T-cell counts. Highly active antiretroviral therapy (HAART) can significantly increase HCV-specific T-cell responses; however, it remains unclear whether the restoration of HCV-specific T cells by HAART is associated with liver injury in these coinfection patients.


METHODS
A total of 32 HIV-1/HCV coinfected patients and 14 HCV monoinfected patients were enrolled, and 13 coinfected patients were initialized HAART and followed up for 6 months. HCV-specific interferon-γ responses to HCV core and NS3A proteins were examined by enzyme-linked immunosorbent spot.


RESULTS
HCV-specific interferon-γ responses to HCV core and NS3A proteins were impaired in HIV-1/HCV-coinfected patients as compared with those in HCV monoinfected patients. The impaired HCV-specific T-cell responses could be efficiently restored during the early phase of HAART, independent of HCV status, and were positively associated with increased CD4 T-cell counts. In addition, this recovery of HCV-specific T-cell responses occurred simultaneously with elevated serum alanine aminotransferase levels in HCV viremic patients and in patients with HCV rebound, but not in HCV nonviremic patients after 6 months of HAART.


CONCLUSIONS
The recovery of HCV-specific T-cell responses by HAART may lead to transient liver injury in patients with HIV-1/HCV coinfection, suggesting that early anti-HCV therapy before HAART may reduce the risk of liver injury and therefore may be beneficial to HIV-1/HCV-coinfected patients.
The Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China.
Fubiao
F
Kang
Weiwei
W
Chen
Xinwei
X
Zhang
Weimin
W
Nie
Junliang
J
Fu
Xiangsheng
X
Xu
Peng
P
Zhao
Xin
X
Zhang
Wengang
W
Li
Fu-Sheng
FS
Wang
Zheng
Z
Zhang
Min
M
Zhao
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D060085:Coinfection; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D018936:Hepatitis C Antigens / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use; D008099:Liver / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology; D019562:Viral Load; D055815:Young Adult
D044966:Anti-Retroviral Agents; D000998:Antiviral Agents; D018936:Hepatitis C Antigens; D012367:RNA, Viral; D014758:Viral Core Proteins; D007371:Interferon-gamma; D000410:Alanine Transaminase