Departments of Medicine and Pathology, VA Medical Center and MetroHealth Medical Center, Case Western Reserve University, ACTG Immunology Support Laboratory, Cleveland Ohio, USA.
Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
J Infect Dis. 2020 Sep 14;222(8):1334-1344. doi: 10.1093/infdis/jiaa254.
Hepatitis C virus (HCV) direct-acting antivirals are highly effective. Less is known about changes in markers of immune activation in persons with human immunodeficiency virus (HIV) in whom a sustained virologic response (SVR) is achieved.
We conducted a nonrandomized clinical trial of 12 or 24 weeks of paritaprevir-ritonavir-ombitasvir plus dasabuvir (PrOD) with or without ribavirin in persons with HCV-1/HIV coinfection suppressed with antiretroviral therapy. Plasma HCV, soluble CD14 (sCD14), interferon-inducible protein 10, soluble CD163 (sCD163), interleukin 6 (IL-6), interleukin 18, monocyte chemoattractant protein (MCP-1), autotaxin (ATX), and Mac2-binding protein (Mac2BP) were measured over 48 weeks.
Participants were treated with PrOD for 12 (n = 9) or 24 (n = 36) weeks; the SVR rate at 12 weeks was 93%. At baseline, cirrhosis was associated with higher ATX and MCP-1, female sex with higher ATX and IL-6, older age with higher Mac2BP, higher body mass index with higher ATX, and HIV-1 protease inhibitor use with higher sCD14 levels. In those with SVR, interferon-inducible protein 10, ATX, and Mac2BP levels declined by week 2, interleukin 18 levels declined by the end of treatment, sCD14 levels did not change, and sCD163, MCP-1, and IL-6 levels changed at a single time point.
During HIV/HCV coinfection, plasma immune activation marker heterogeneity is in part attributable to age, sex, cirrhosis, body mass index, and/or type of antiretroviral therapy. HCV treatment with paritaprevir-ritonavir-ombitasvir plus dasabuvir is highly effective and is associated with variable rate and magnitude of decline in markers of immune activation.
NCT02194998.
丙型肝炎病毒（HCV）直接作用抗病毒药物具有高度疗效。在获得持续病毒学应答（SVR）的人类免疫缺陷病毒（HIV）感染者中，关于免疫激活标志物变化的了解较少。
我们进行了一项非随机临床试验，对接受抗逆转录病毒治疗抑制的 HCV-1/HIV 合并感染患者，使用帕立瑞韦/利托那韦/奥比他韦加达卡他韦（PrOD）进行 12 或 24 周治疗，联合或不联合利巴韦林。在 48 周内测量血浆 HCV、可溶性 CD14（sCD14）、干扰素诱导蛋白 10、可溶性 CD163（sCD163）、白细胞介素 6（IL-6）、白细胞介素 18、单核细胞趋化蛋白 1（MCP-1）、自分泌运动因子（ATX）和 Mac2 结合蛋白（Mac2BP）。
参与者接受 PrOD 治疗 12（n = 9）或 24 周（n = 36）；12 周时 SVR 率为 93%。基线时，肝硬化与 ATX 和 MCP-1 水平升高相关，女性与 ATX 和 IL-6 水平升高相关，年龄较大与 Mac2BP 水平升高相关，体重指数较高与 ATX 水平升高相关，HIV-1 蛋白酶抑制剂使用与 sCD14 水平升高相关。在获得 SVR 的患者中，干扰素诱导蛋白 10、ATX 和 Mac2BP 水平在第 2 周下降，白细胞介素 18 水平在治疗结束时下降，sCD14 水平不变，sCD163、MCP-1 和 IL-6 水平仅在一个时间点发生变化。
在 HIV/HCV 合并感染中，血浆免疫激活标志物异质性部分归因于年龄、性别、肝硬化、体重指数和/或抗逆转录病毒治疗类型。使用帕立瑞韦/利托那韦/奥比他韦加达卡他韦治疗 HCV 非常有效，并与免疫激活标志物的下降速度和幅度相关。
NCT02194998。
