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Hepatitis C Virus Cure in Human Immunodeficiency Virus Coinfection Dampens Inflammation and Improves Cognition Through Multiple Mechanisms.
The Journal of Infectious Diseases ( IF 5.0 ) Pub Date : 2020-03-11 , DOI: 10.1093/infdis/jiaa109
Bing Sun 1 , Linda Abadjian 2 , Alexander Monto 3, 4 , Heather Freasier 3 , Lynn Pulliam 1, 3, 4
Affiliation  

Background
Chronic inflammation in HIV/HCV coinfection increases cognitive impairment. With newer direct-acting antiviral therapies for HCV, our objective was to determine if chronic inflammation would be decreased and cognition improved with HCV sustained viral response (SVR) in coinfection.
Methods
We studied 4 groups longitudinally, 7 HCV monoinfected and12 HIV/HCV coinfected before and after treatment for HCV, 12 HIV monoinfected and 9 healthy controls. We measured monocyte activation and gene expression, monocyte-derived exosome miRNAs expression, plasma inflammation and cognitive impairment before and after therapy.
Results
Plasma sCD163 and neopterin were decreased in HCV mono and coinfected persons. Blood CD16+ monocytes were decreased in coinfection after HCV treatment. Global deficit score improved 25% in coinfection with the visual learning/memory domain the most improved. HCV SVR decreased monocyte interferon genes MX1, IFI27 and CD169 in coinfection and MX1, LGALS3BP and TNFAIP6 in HCV monoinfection. Monocyte exosomes from coinfected persons increased in miR-19a, miR-221 and miR-223, all associated with decreasing inflammation and NF-κB activation.
Conclusions
HCV cure in coinfection brings monocyte activation to levels of HIV alone. Cognitive impairment is significantly improved with cure but not better than HIV infection alone strongly suggesting that cognitive impairment was driven by both HIV and HCV.


中文翻译:

人类免疫缺陷病毒合并感染中的丙型肝炎病毒治愈可减轻炎症并通过多种机制改善认知。

背景
HIV / HCV合并感染中的慢性炎症会增加认知障碍。使用更新的HCV直接作用抗病毒疗法,我们的目标是确定在合并感染中使用HCV持续病毒应答(SVR)是否可以减少慢性炎症并改善认知。
方法
我们纵向研究了4组,分别在治疗HCV前后分别感染了7例HCV和12例HIV / HCV,以及12例HIV / HCV。我们测量了治疗前后的单核细胞激活和基因表达,单核细胞来源的外泌体miRNA表达,血浆炎症和认知障碍。
结果
丙型肝炎病毒单感染者和合并感染者血浆sCD163和新蝶呤降低。HCV治疗后的合并感染中血液CD16 +单核细胞减少。在视觉感染/记忆领域改善最大的合并感染中,全球缺陷评分提高了25%。HCV SVR在合并感染中降低了单核细胞干扰素基因MX1,IFI27和CD169,在HCV单一感染中降低了MX1,LGALS3BP和TNFAIP6。来自合并感染者的单核细胞外泌体在miR-19a,miR-221和miR-223中增加,所有这些都与炎症减少和NF-κB活化有关。
结论
合并感染中的HCV治愈使单核细胞活化达到单独的HIV水平。治愈后认知障碍得到显着改善,但并不比仅HIV感染好,这强烈表明认知障碍是由HIV和HCV共同驱动的。
更新日期:2020-03-12
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