Daclatasvir plus Sofosbuvir for Previously Treated or Untreated Chronic HCV Infection
Daclatasvir plus Sofosbuvir for Previously Treated or Untreated Chronic HCV Infection
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DOI：
10.1056/nejmoa1306218
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发表时间：
2014-01-16
影响因子：
158.5
通讯作者：
Grasela, Dennis M.
中科院分区：
文献类型：
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作者：
Sulkowski, Mark S.;Gardiner, David F.;Grasela, Dennis M.
背景：慢性丙型肝炎病毒（HCV）感染患者需要全口服联合治疗。我们评估了daclatasvir（一种HCV NS5A复制复合体抑制剂）和sofosbuvir（一种核苷酸类似物HCV NS5B聚合酶抑制剂）在HCV基因型1、2或3感染患者中的作用。方法在这项开放标签研究中，我们最初随机分配了44名未经治疗的HCV基因型1感染患者和44名HCV基因型2或3感染患者，给予daclatasvir 60mg /天口服一次，加上索非布韦400mg /天口服一次，联合或不联合利巴韦林，持续24周。该研究扩大到123名额外的基因型感染患者，他们被随机分配到daclatasvir + sofosbuvir，有或没有利巴韦林，为期12周（82名先前未治疗的患者）或24周（41名先前使用telaprevir或boceprevir +聚乙二醇干扰素-利巴韦林的病毒学失败的患者）。主要终点是持续的病毒学应答(HCV RNA水平为
BackgroundAll-oral combination therapy is desirable for patients with chronic hepatitis C virus (HCV) infection. We evaluated daclatasvir (an HCV NS5A replication complex inhibitor) plus sofosbuvir (a nucleotide analogue HCV NS5B polymerase inhibitor) in patients infected with HCV genotype 1, 2, or 3.MethodsIn this open-label study, we initially randomly assigned 44 previously untreated patients with HCV genotype 1 infection and 44 patients infected with HCV genotype 2 or 3 to daclatasvir at a dose of 60 mg orally once daily plus sofosbuvir at a dose of 400 mg orally once daily, with or without ribavirin, for 24 weeks. The study was expanded to include 123 additional patients with genotype 1 infection who were randomly assigned to daclatasvir plus sofosbuvir, with or without ribavirin, for 12 weeks (82 previously untreated patients) or 24 weeks (41 patients who had previous virologic failure with telaprevir or boceprevir plus peginterferon alfa-ribavirin). The primary end point was a sustained virologic response (an HCV RNA level of