Article

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

1The Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing 100039, China 2Research Center of Biological Therapy, Beijing 302 Hospital, Beijing 100039, China.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.39). 10/2012; 62(2). DOI: 10.1097/QAI.0b013e3182752d20
Source: PubMed

ABSTRACT OBJECTIVES:: HIV-1/HCV co-infection 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 co-infection patients. METHODS:: A total of 32 HIV-1/HCV co-infected patients and 14 HCV mono-infected patients were enrolled, and 13 co-infected 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 co-infected patients as compared with those in HCV mono-infected 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 ALT levels in HCV viremic patients and in patients with HCV rebound, but not in HCV non-viremic patients after 6 months of HAART. CONCLUSION:: The recovery of HCV-specific T cell responses by HAART may lead to transient liver injury in patients with HIV-1/HCV co-infection, suggesting that early anti-HCV therapy before HAART may reduce the risk of liver injury and therefore may be beneficial to HIV-1/HCV co-infected patients.

0 Followers
 · 
54 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite significant reductions in morbidity and mortality secondary to availability of effective combination anti-retroviral therapy (cART), human immunodeficiency virus (HIV) infection still accounts for 1.5 million deaths annually. The majority of deaths occur in sub-Saharan Africa where rates of opportunistic co-infections are disproportionately high. In this review, we discuss the immunopathogenesis of five common infections that cause significant morbidity in HIV-infected patients globally. These include co-infection with Mycobacterium tuberculosis, Cryptococcus neoformans, hepatitis B virus, hepatitis C virus, and Plasmodium falciparum. Specifically, we review the natural history of each co-infection in the setting of HIV, the specific immune defects induced by HIV, the effects of cART on the immune response to the co-infection, the pathogenesis of immune restoration disease (IRD) associated with each infection, and advances in the areas of prevention of each co-infection via vaccination. Finally, we discuss the opportunities and gaps in knowledge for future research.
    Immunological Reviews 07/2013; 254(1):114-42. DOI:10.1111/imr.12063 · 12.91 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: scitranslmed.3008195 , 246ra98 (2014); 6 Sci Transl Med et al. Kenneth E. Sherman HCV/HIV co-infected patients Modulation of HCV replication after combination antiretroviral therapy in Editor's Summary infection. HIV suppression with antiretroviral medications plays an important role in the management of those with HCV and HIV This process is highly modulated by responses of the interferon-responsive gene family. The findings suggest that viral replication and evidence of liver injury. Over time, however, HIV suppression leads to reduced HCV replication. biological effects. They show that the initial response to effective HIV treatment results in a transient increase in HCV try and unravel some of these et al. virus (HCV). In a new study of patients co-infected with HCV and HIV, Sherman There is a complex interaction of biological effects when patients are infected with both HIV and the hepatitis C
    Science translational medicine 07/2014; 6(246):98. · 14.41 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The hepatitis C virus (HCV) is an important contributor to morbidity and mortality in patients co-infected with HIV. Co-infection results in increased HCV replication and more rapid rates of liver disease progression. The effect of HIV combination antiretroviral therapy (cART) on HCV replication has not been studied in depth. To address this issue, we enrolled a small cohort of HCV/HIV co-infected patients into a cART initiation trial and used dynamic modeling combined with evaluation of immune responses and microarray profiles to determine how effective treatment of HIV affects HCV. Treatment with cART resulted in increased HCV replication and increased alanine aminotransferase (ALT) in a subset of patients. Subjects with evidence of hepatic injury (increased ALT) were more likely to have HCV-specific immune responses directed against HCV epitopes. Over time, HCV viral loads declined. Reproducible and biologically important gene expression changes occurred in co-infected patients who underwent successful cART. The effective suppression of HIV by cART initiated a cascade of early and late events in treated patients. Early events involving down-regulation of interferon-stimulated genes may have led to transiently increased viral replication and hepatic injury. At later time points, HCV viral load declined to levels comparable to those seen in the setting of HCV monoinfection. These findings support early antiretroviral therapy in those with HCV/HIV co-infection.
    Science translational medicine 07/2014; 6(246):246ra98. DOI:10.1126/scitranslmed.3008195 · 14.41 Impact Factor
Show more