Direct-acting antivirals (DAA) targeting hepatitis C virus (HCV) have revolutionized outcomes in HIV co-infection. We examined early events in liver and plasma through A5335S, a substudy of trial A5329 (paritaprevir/ritonavir, ombitasvir, dasabuvir, with ribavirin) that enrolled chronic genotype 1a HCV-infected persons co-infected with suppressed HIV: 5/6 treatment-naïve enrollees completed A5335S. Mean baseline plasma HCV RNA=6.7 log₁₀ IU/mL and changed by -4.1 log₁₀ IU/mL by Day 7. In liver, laser capture microdissection was used to quantify HCV. At liver biopsy 1, mean (95% CI) %HCV-infected cells=25.2% (7.4%, 42.9%), correlating with plasma HCV RNA (Spearman rank correlation r=0.9); biopsy 2 (Day 7 in 4/5 participants) mean (95% CI) %HCV-infected cells=1.0% (0.2%, 1.7%)(p<0.05 for change), and DAAs were detectable in liver. Plasma CXCL10 concentrations changed by mean=-160 pg/mL/day at 24 hours, but no further after Day 4. We conclude that HCV infection is rapidly cleared from liver with DAA leaving <2% HCV-infected hepatocytes at Day 7. We extrapolate that HCV eradication could occur in these participants by 63 days, although immune activation might persist. Single-cell longitudinal estimates of HCV clearance from liver have never been reported previously and could be applied to estimating the minimum treatment duration required for HCV infection.

中文翻译：

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人类免疫缺陷病毒合并感染丙型肝炎直接抗病毒药物期间的肝内病毒动力学：艾滋病临床试验组 A5335S 子研究。

针对丙型肝炎病毒 (HCV) 的直接作用抗病毒药物 (DAA) 彻底改变了 HIV 合并感染的结果。我们通过 A5335S 检查了肝脏和血浆中的早期事件，该试验是 A5329 试验（paritaprevir/ritonavir、ombitasvir、dasabuvir 和利巴韦林）的子研究，该试验招募了慢性基因型 1a HCV 感染者合并感染抑制 HIV：5/6 初治参加者完成了 A5335S。平均基线血浆 HCV RNA=6.7 log ₁₀ IU/mL，变化 -4.1 log ₁₀第 7 天 IU/mL。在肝脏中，激光捕获显微切割用于量化 HCV。在肝活检 1 中，平均 (95% CI) %HCV 感染细胞=25.2% (7.4%, 42.9%)，与血浆 HCV RNA 相关（Spearman 秩相关 r=0.9）；活检 2（4/5 参与者的第 7 天）平均 (95% CI) %HCV 感染细胞=1.0%（0.2%，1.7%）（变化 p<0.05），并且在肝脏中可检测到 DAA。血浆 CXCL10 浓度在 24 小时时平均变化 = -160 pg/mL/天，但在第 4 天后没有变化。我们得出结论，HCV 感染迅速从肝脏中清除，DAA 在第 7 天留下 <2% HCV 感染的肝细胞。我们推断这些参与者可能会在 63 天内根除 HCV，尽管免疫激活可能会持续存在。