Longitudinal Assessment of Multiple Immunological and Inflammatory Parameters during Successful DAA Therapy in HCV Monoinfected and HIV/HCV Coinfected Subjects

HCV 单一感染者和 HIV/HCV 合并感染者中 DAA 治疗成功期间多项免疫和炎症参数的纵向评估

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作者:Paola Zuccalà, Tiziana Latronico, Raffaella Marocco, Stefano Savinelli, Serena Vita, Fabio Mengoni, Tiziana Tieghi, Cosmo Borgo, Blerta Kertusha, Anna Carraro, Gabriella D'Ettorre, Vincenzo Vullo, Claudio Maria Mastroianni, Grazia Maria Liuzzi, Miriam Lichtner

Abstract

In the direct-acting antiviral (DAA) era, it is important to understand the immunological changes after HCV eradication in HCV monoinfected (mHCV) and in HIV/HCV coinfected (HIV/HCV) patients. In this study, we analyzed sub-populations of monocytes, dendritic cells (DCs), T-lymphocytes and inflammatory biomarkers following initiation of DAA in 15 mHCV and 16 HIV/HCV patients on effective antiretroviral therapy at baseline and after sustained virological response at 12 weeks (SVR12). Fifteen age- and sex-matched healthy donors (HD) were enrolled as a control group. Activated CD4+ and CD8+ T-lymphocytes, mDCs, pDCs, MDC8 and classical, non-classical and intermediate monocytes were detected using flow cytometry. IP-10, sCD163 and sCD14 were assessed by ELISA while matrix metalloproteinase-2 (MMP-2) was measured by zymography. At baseline, increased levels of IP-10, sCD163 and MMP-2 were found in both HIV/HCV and mHCV patients compared to HD, whereas sCD14 increased only in HIV/HCV patients. After therapy, IP-10, sCD163 and sCD14 decreased, whereas MMP-2 persistently elevated. At baseline, activated CD8+ T-cells were high in HIV/HCV and mHCV patients compared to HD, with a decrease at SVR12 only in HIV/HCV patients. Activated CD4+ T-cells were higher in HIV/HCV patients without modification after DAAs therapy. These results suggest complex interactions between both viruses and the immune system, which are only partially reversed by DAA treatment.

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