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.
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.
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.
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.
[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.
[Show abstract][Hide abstract] ABSTRACT: Hepatitis C virus (HCV) is an important cause of acute and chronic hepatitis which is a disorder with a high worldwide prevalence. HCV core protein was considered as immunogenic counterpart of the HCV vaccine and it is an ideal candidate for HCV vaccine. Since cytokines such as IL-6, TNF-alpha and IFN-Gamma are responsible for the prevention of viral infection, this study aimed to evaluate the effectiveness of HCV core protein as a vaccine. Ten BALB/c mice were immunized with HCV core protein and after 42 days the splenocytes were isolated and the IL-6 and INF-gamma secretion were measured using ELISpot technique, at the same time TNF-alpha was determined by ELISA in the sera. The MTT assay was done to assess the viability of the cultured splenocytes. For evaluating the humoral immune response against the recombinant HCV core protein the DOT Blot test was used. Data was compared using one-way ANOVA test and significant results were considered at p < 0.05. In the present study the IL-6, INF-gamma and TNF-alpha levels were dramatically higher in the immunized mice compared to the control group (respectively, 22.9 +/- 1.26; 18.53 +/- 3.87; 53.96 +/- 4.54 and p < 0.05). The immunized mice with recombinant HCV core protein showed higher amount of IL-6, INF-gamma and TNF-alpha in the current study. Since the level of IL-6, TNF-alpha and IFN-gamma is high in patients with acute HCV infection, thus a vaccine which could stimulate the secretion of these cytokines in advance may have a preventive role.
Pakistan Journal of Biological Sciences 12/2013; 16(24):2041-5. DOI:10.3923/pjbs.2013.2041.2045
[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. · 15.84 Impact Factor
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