Virology
Characteristics of the cellular immune response in HIV/HCV patients with hemophilia during peginterferon/ribavirin therapy in southern China,☆☆

https://doi.org/10.1016/j.diagmicrobio.2013.07.021Get rights and content

Abstract

Objective

The objectives of the study are to characterize the cellular immune response in hepatitis C virus (HCV) genotype 1 and HIV co-infected patients with hemophilia in southern China during treatment with interferon and ribavirin and to study its correlation with the virologic response (VR). Thirty-six HCV genotype 1 and HIV co-infected patients with hemophilia in southern China were enrolled into the study. Using an ELISpot assay, HCV antigen-specific interferon (IFN) γ, interleukin (IL) 2, IL-4, and IL-10 secreting cells were measured in peripheral blood mononuclear cells. Single nucleotide polymorphisms of IL28B were determined, and immunological, virologic, and clinical variables were collected to identify factors associated with HCV-sustained VR (SVR) at week 72 after treatment. At baseline, there were no significant differences in IFN-γ and IL-2 mediated immune responses in subjects with VR versus non-responders. Higher IL-10 specific responses to NS3 were observed in VR patients. Subjects who had significant decreases in IL-10 responses at week 72 compared with baseline for NS3 and NS5 were more likely to be VR. In SVR, IL-2 production decreased moderately, and the levels of IL-4 were low throughout. The main correlation for SVR in genotype-l infected subjects was sustained HCV-specific IFN-γ responses through the whole 72-week period. In subjects with HIV and HCV co-infection combined with hemophilia, IL28B genotype CC, a decrease in HCV specific IL-l0 and IL-2 responses, and the maintenance of IFN-γ responses during treatment were associated with a 12- or 72-week VR.

Section snippets

Background

Hepatitis C is a major cause of morbidity and death in HIV-infected individuals (Bambha et al., 2012, Mocroft et al., 2012). As reported, 9–40% HIV patients are co-infected with hepatitis C virus (HCV) (Greub et al., 2000), and HCV infection rate reaches 85% in HIV patients with hemophilia (Sterling et al., 2010). Co-infection with HIV accelerates the progression to liver cirrhosis. Cellular immune responses, crucial for the control of HCV infection (Rohrbach et al., 2010), are weak in chronic

Patients

Thirty-six HIV/HCV co-infected patients with hemophilia in Shanghai Public Health Clinical Center from 2007 to 2009 were enrolled in this study, their ages ranging from 19 to 51 years old, sex ratio of 1:1, all the patients were HBV DNA negative and infected with HCV genotype 1b.

Clinical characteristics of the study group are described in Table 1. Age and ethnicity were similar among the patient groups.

All patients were treated by combined antiviral therapy for HCV. They were given

Patient characteristics and SVR

Thirty-six HIV/HCV co-infected patients with HCV genotype 1 had SVR rate of 27% (10/36) compared to 45% in mono HCV genotype 1 infected group. SVR in HIV/HCV co-infected patients was not associated with the immune state and CD4+ cell counts of patients; it increased with inflammatory scores of liver histology but had no obvious correlation (P > 0.05). SVR rate in IL28B genotype CC is 41% (7/17); it is much higher than that (16%, 3/19) in genotype non-CC in HIV and HCV genotype 1 co-infected

Discussion

In HCV monoinfection, combination antiviral therapy has resulted in SVR rates ranging from 45% to 55% in groups with genotypes 1 or 4 (François et al., 2009). In HCV/HIV co-infection, SVR rates in patients infected with genotype 1 are lower than those infected with genotype 2 or 3.

The incidence of hemophilia is higher than 85% in HIV/HCV co-infected patients, and it is necessary to give combination antiviral therapy for HCV to these patients. In China, the most common genotypes of HCV infection

Acknowledgment

This work was supported by Fudan University, China.

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    • Influence of IL28B gene polymorphisms on PegINF-RBV-mediated HCV clearance in HIV-HCV co-infected patients: A meta-analysis

      2021, Meta Gene
      Citation Excerpt :

      The research articles were further stratified according to the SNPs, HCV genotypes, and treatment response (SVR/RVR). There were 34 and 12 studies that examined the association of IL28B rs12979860 with SVR (Abu Dayyeh et al., 2011; Amorosa et al., 2013; Bruno et al., 2015; Corchado et al., 2014; de Castellarnau et al., 2012; Di Lello et al., 2013; Franco et al., 2014; Keane et al., 2013; Labarga et al., 2014, Labarga et al., 2012, Labarga et al., 2011; López-Cortés et al., 2012; Mandorfer et al., 2013b, Mandorfer et al., 2013a; Matas and Picornell, 2014; Mira et al., 2012; Nattermann et al., 2011; Neukam et al., 2013b, Neukam et al., 2013a, Neukam et al., 2012; Osinusi et al., 2012; Pineda et al., 2010; Rallon et al., 2013, Rallon et al., 2012; Rallón et al., 2011, Rallón et al., 2010; Antonio Rivero-Juarez et al., 2013b; A. Rivero-Juarez et al., 2013b; Sehgal et al., 2014; Stenkvist et al., 2013; Sticchi et al., 2015; Torres-Cornejo et al., 2014; Vispo et al., 2012; Yingying et al., 2014; Zeremski et al., 2013) and RVR (Corchado et al., 2014; Keane et al., 2013; López-Cortés et al., 2012; Mandorfer et al., 2013a; Matas and Picornell, 2014; Neukam et al., 2013a; Rallón et al., 2011; Antonio Rivero-Juarez et al., 2013b; Rivero-Juarez et al., 2012; Rivero-Juárez et al., 2012; Stenkvist et al., 2013; Torres-Cornejo et al., 2014), respectively, for all the HCV genotypes. The studies that evaluated the association between the other SNPs and SVR are as follows: 6 studies for rs8099917 (Aparicio et al., 2010; Bruno et al., 2015; de Castellarnau et al., 2012; Fernández-Rodríguez et al., 2013; Liu et al., 2015; Sticchi et al., 2015), and 4 studies for rs12980275 (Fernández-Rodríguez et al., 2014, Fernández-Rodríguez et al., 2013; Guzmán-Fulgencio et al., 2014; Pineda-Tenor et al., 2014). (

    Competing interests: The authors declare that they have no competing interests.

    ☆☆

    Authors' contributions: LY designed the experiment and drafted the manuscript. WJR collected the specimen and performed the statistical analysis. LJ carried out most experiments and participated in its design. All authors read and approved the final manuscript.

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