Randomized trial of daclatasvir and asunaprevir with or without PegIFN/RBV for hepatitis C virus genotype 1 null responders
Randomized trial of daclatasvir and asunaprevir with or without PegIFN/RBV for hepatitis C virus genotype 1 null responders
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DOI：
10.1016/j.jhep.2013.10.019
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发表时间：
2014-03-01
影响因子：
25.7
通讯作者：
Pasquinelli, Claudio
中科院分区：
文献类型：
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作者：
Lok, Anna S.;Gardiner, David F.;Pasquinelli, Claudio
背景与目的：慢性丙型肝炎病毒（HCV）感染和既往无效应答（≥ 12周的聚乙二醇干扰素/RBV）患者的选择有限。我们评估了达卡他韦加一次或两次，每天阿那匹韦在非阿尔茨海默病基因型1 null respons.Methods：在这个随机化，2a期，开放标签，24周的治疗研究，101例患者接受达卡他韦（60毫克），每天一次。此外，38名基因型1b患者接受了asunaprevir（200 mg）每日两次（DUAL A1）或每日一次（DUAL A2）; 36名基因型1a和5名基因型1b患者接受了asunaprevir每日两次（QUAD B1）或每日一次（QUAD B2）+PegIFN/RBV; 18名基因型1a和4名基因型1b患者接受了asunaprevir每日两次+利巴韦林（TRIPLE B3）。主要终点是治疗后12周检测不到HCV RNA（持续病毒学应答，SVR 12）。结果：在所有组中，平均HCV RNA>= 6 log IU/ml，99%的患者具有非CC IL 28 B基因型。SVR 12率分别为78%（A1）、65%（A2）、95%（B1）和95%（B2）。在B3中，大多数基因型lla患者经历了病毒学突破。最常见的不良反应是头痛、腹泻和乏力。3-4级转氨酶升高是罕见的，而不是治疗limited.Conclusions：在基因型1无效应答者，达卡他韦加每日两次asunaprevir DUAL治疗是有效的大多数基因型1b患者，和达卡他韦，asunaprevir，和PegIFN/RBV QUAD治疗是有效的几乎所有基因型1a和1b患者，但无论是DUAL还是TRIPLE治疗是有效的基因型1a患者。对于基因型1无效应答者，应根据亚型定制无干扰素方案，包括达卡他韦和每日两次asunaprevir。(C)2013年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background & Aims: Patients with chronic hepatitis C virus (HCV) infection and prior null response (= 12 weeks of PegIFN/RBV) have limited options. We evaluated daclatasvir plus once- or twice-daily asunaprevir in non-cirrhotic genotype 1 null responders.Methods: In this randomized, phase 2a, open-label, 24-week treatment study, 101 patients received daclatasvir (60 mg) once-daily. In addition, 38 genotype 1b patients received asunaprevir (200 mg) twice- (DUAL A1) or once-daily (DUAL A2); 36 genotype 1a and 5 genotype 1b patients received asunaprevir twice- (QUAD B1) or once-daily (QUAD B2) plus PegIFN/RBV; and 18 genotype 1a and 4 genotype 1b patients received asunaprevir twice-daily plus ribavirin (TRIPLE B3). The primary end-point was undetectable HCV RNA 12 weeks post-treatment (sustained virologic response, SVR12).Results: Across all groups, mean HCV RNA was >= 6 log IU/ml, and 99% of patients had a non-CC IL28B genotype. SVR12 rates were 78% (A1), 65% (A2), 95% (B1), and 95% (B2). In B3, most genotype l1a patients experienced virologic breakthrough. The most com mon adverse events were headache, diarrhea, and asthenia. Grade 3-4 aminotransferase elevations were infrequent and not treatment-limiting.Conclusions: In genotype 1 null responders, daclatasvir plus twice-daily asunaprevir DUAL therapy is effective for most genotype 1b patients, and daclatasvir, asunaprevir, and PegIFN/RBV QUAD therapy is effective for nearly all genotype 1a and 1b patients; but neither DUAL nor TRIPLE therapy is effective for genotype 1a patients. Interferon-free regimens including daclatasvir and twice-daily asunaprevir for genotype 1 null responders should be tailored to subtype. (C) 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.