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. 2018 Sep;42(4):319-329.
doi: 10.1016/j.clinre.2017.11.006. Epub 2017 Dec 24.

Direct-acting antiviral therapy enhances total CD4+ and CD8+ T-cells responses, but does not alter T-cells activation among HCV mono-infected, and HCV/HIV-1 co-infected patients

Saeid Najafi Fard  1 , Ivan Schietroma  2 , Giuseppe Corano Scheri  2 , Noemi Giustini  2 , Sara Serafino  2 , Eugenio Nelson Cavallari  2 , Claudia Pinacchio  2 , Gabriella De Girolamo  2 , Giancarlo Ceccarelli  3 , Carolina Scagnolari  4 , Vincenzo Vullo  2 , Gabriella d'Ettorre  3
Affiliations

Direct-acting antiviral therapy enhances total CD4+ and CD8+ T-cells responses, but does not alter T-cells activation among HCV mono-infected, and HCV/HIV-1 co-infected patients

Saeid Najafi Fard et al. Clin Res Hepatol Gastroenterol. 2018 Sep.

Abstract

Aim: Chronic immune activation and poor T-cell immune response are strongly associated with disease progression and pathogenesis of both hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-1 infections. Little is known about the impact of anti-HCV Interferon (IFN)-free direct-acting antiviral (DAA) therapy on the systemic T-cells activation and patterns of peripheral T-cells producing pro-inflammatory cytokines.

Patients and methods: Forty-five subjects including 18 HCV mono-infected, 17 HCV/HIV-1 co-infected patients under antiretroviral therapy (ART), and 10 healthy controls (HCs) were recruited. Blood samples were collected at baseline (T0) and 12 weeks after the end of DAA therapy (T1). Cell phenotypes (CD3, CD4, CD8), activation markers (CD38 and HLA-DR), and frequency of IFN-γ, interleukin (IL)-17, and IL-22 producing CD4+ and CD8+ T-cells were measured by flow cytometry. Plasma levels of related cytokines were also measured by enzyme-linked immunosorbent assay (ELISA).

Results: Both HCV, and HCV/HIV-1 patients before and after therapy, showed significant higher percentages of any T-cell subset expressing CD38 and/or HLA-DR compared to HCs. No differences were observed in T-cells activation at T1 compared to T0 in patient groups, and when HCV patients were compared to HCV/HIV-1 group (P>0.05). After therapy, the potential of total circulating T helper (Th) and T cytotoxic (Tc) cells producing IFN-γ, IL-17, and IL-22 were increased. Plasma level of IFN-γ at baseline was showed difference compared to HCs, and significantly reduced after therapy (P<0.05).

Conclusion: Total T-cells immune response enhances after therapy, however, the state of immune activation may remain elevated for a longtime after the end of treatment and contribute to post-Sustained Virologic Response (SVR) consequences.

Keywords: Direct-acting antiviral; Hepatitis C virus; Human immunodeficiency virus-1; Immune activation; Intracellular cytokine assay; T-cell.

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