Intrahepatic Viral Kinetics During Direct-Acting Antivirals for Hepatitis C in Human Immunodeficiency Virus Coinfection: The AIDS Clinical Trials Group A5335S Substudy
Intrahepatic Viral Kinetics During Direct-Acting Antivirals for Hepatitis C in Human Immunodeficiency Virus Coinfection: The AIDS Clinical Trials Group A5335S Substudy
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DOI：
10.1093/infdis/jiaa126
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发表时间：
2020-08-15
影响因子：
6.4
通讯作者：
Talal，Andrew H.
中科院分区：
文献类型：
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作者：
Balagopal，Ashwin;Smeaton，Laura M.;Talal，Andrew H.
针对丙型肝炎病毒（HCV）的直接作用抗病毒药物（DAAs）已经彻底改变了人类免疫缺陷病毒（HIV）合并感染的结果。我们通过A5335S检查肝脏和血浆中的早期事件，A5335S是试验A5329 （paritaprevir/ritonavir, ombitasvir， dasabuvir和利巴韦林）的一项亚研究，该试验招募了慢性基因型1a hcv感染合并抑制HIV的患者：6名未接受治疗的入组者中有5名完成了A5335S治疗。结果平均基线血浆HCV核糖核酸(RNA) = 6.7 log10IU/mL，到第7天改变为- 4.1 log10IU/mL。在肝脏，激光捕获显微解剖用于定量HCV。肝活检1时，HCV感染细胞的平均% = 25.2%(95%可信区间[CI]， 7.4%-42.9%)，与血浆HCV RNA相关（Spearman秩相关r = 0.9）；在活检2（5名参与者中有4名第7天），平均% hcv感染细胞= 1.0% (95% CI, 0.2%-1.7%) （P< 0.05）。肝脏中检测到DAAs。血浆C-X-C基序趋化因子10 （CXCL10）浓度在24小时内平均变化为- 160 pg/mL /天，但在第4天之后没有进一步变化。结论：HCV感染在第7天迅速从肝脏中清除，DAA只留下小于2%的HCV感染肝细胞。我们推断，尽管免疫激活可能持续存在，但这些参与者在63天后可能发生HCV根除。HCV肝脏清除率的单细胞纵向估计以前从未报道过，可用于估计HCV感染所需的最短治疗时间。
BackgroundDirect-acting antivirals (DAAs) targeting hepatitis C virus (HCV) have revolutionized outcomes in human immunodeficiency virus (HIV) coinfection.MethodsWe 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 coinfected with suppressed HIV: 5 of 6 treatment-naive enrollees completed A5335S.ResultsMean baseline plasma HCV ribonucleic acid (RNA) = 6.7 log10IU/mL and changed by −4.1 log10IU/mL by Day 7. In liver, laser capture microdissection was used to quantify HCV. At liver biopsy 1, mean %HCV-infected cells = 25.2% (95% confidence interval [CI], 7.4%–42.9%), correlating with plasma HCV RNA (Spearman rank correlation r = 0.9); at biopsy 2 (Day 7 in 4 of 5 participants), mean %HCV-infected cells = 1.0% (95% CI, 0.2%–1.7%) (P< .05 for change), and DAAs were detectable in liver. Plasma C-X-C motif chemokine 10 (CXCL10) concentrations changed by mean = −160 pg/mL per day at 24 hours, but no further after Day 4.ConclusionsWe 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.