Background Hepatitis C virus (HCV) infects nearly one-fourth of people with HIV (PWH). The role of direct-acting antivirals (DAAs) on immune activation in PWH and HCV is poorly understood. Methods We quantified plasma HCV RNA and CXCL10 in persons with HCV mono- versus HIV/HCV co-infection receiving Sofosbuvir-Velpatasvir. Single-cell laser capture was applied to liver biopsies obtained before and within 4-7 days of DAA initiation to estimate HCV clearance and changes in interferon stimulated genes (ISGs). Results We enrolled ten people with chronic genotype 1a HCV: five were PWH. Median (min-max) ages at enrollment were 55.5 (28-66) years, five were women, and eight were African American. At baseline, plasma HCV RNA levels were 6.36 (5.68-7.93) log10 IU/mL; all had transient elastography liver stiffness < 9 kPa. CD4+ T cell counts in PWH were 768 (244-1136) cells/µL. All had suppressed HIV viremia on antiretrovirals. First and second phase plasma HCV RNA kinetics were not different between groups. Median (min-max) proportions of infected hepatocytes at biopsy 1 were 0.06 (0.01-0.59) in HCV mono- and 0.21 (0.04-0.87) in HIV/HCV co-infection and did not differ. Participants had lower intracellular HCV RNA levels at biopsy 2, but not differentially by HIV status. CXCL10 levels declined in both groups but was higher in co- than in mono-infection even at the end of treatment. Proportion of cells expressing ISGs diminished in mono- but increased in co-infection. Conclusion Whereas DAAs rapidly cleared intrahepatic HCV in both groups, immune activation was slower to diminish in PWH. Residual immune activation in PWH warrants further exploration.

中文翻译：

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直接作用的抗病毒药物可迅速从 HIV 感染者的肝脏中根除 HCV，但不能完全逆转免疫激活


背景 丙型肝炎病毒 （HCV） 感染了近四分之一的 HIV 感染者 （PWH）。直接作用抗病毒药物 （DAA） 对 PWH 和 HCV 免疫激活的作用知之甚少。方法 我们量化了接受 Sofosbuvir-Velpatasvir 的 HCV 单一感染与 HIV/HCV 合并感染者的血浆 HCV RNA 和 CXCL10。将单细胞激光捕获应用于 DAA 开始之前和之后 4-7 天内获得的肝活检，以估计 HCV 清除率和干扰素刺激基因 （ISG） 的变化。结果 我们招募了 10 名慢性基因型 1a HCV 患者： 5 名是 PWH。入组时的中位 （min-max） 年龄为 55.5 （28-66） 岁，其中 5 名是女性，8 名是非裔美国人。基线时，血浆 HCV RNA 水平为 6.36 （5.68-7.93） log10 IU/mL;所有患者均具有瞬时弹性成像肝脏硬度 < 9 kPa。PWH 中的 CD4+ T 细胞计数为 768 （244-1136） 个细胞/μL。所有药物均使用抗逆转录病毒药物抑制了 HIV 病毒血症。第一和第二期血浆 HCV RNA 动力学在组间没有差异。活检 1 时感染肝细胞的中位 （min-max） 比例在 HCV 单一感染中为 0.06 （0.01-0.59），在 HIV/HCV 混合感染中为 0.21 （0.04-0.87），没有差异。参与者在活检 2 时细胞内 HCV RNA 水平较低，但 HIV 状态没有差异。即使在治疗结束时，两组的 CXCL10 水平均下降，但 co- 水平高于单一感染。表达 ISGs 的细胞比例在单一感染中减少，但在混合感染中增加。结论 虽然 DAAs 在两组中都能迅速清除肝内 HCV，但 PWH 的免疫激活减弱较慢。PWH 中的残留免疫激活值得进一步探索。