（旧金山）在2013感染性疾病周上报告的一个研究中，感染1型丙肝病毒的患者使用daclatasvir（NS5A抑制剂，DCV）, asunaprevir（NS3抑制剂,ASV）和一种非核苷类NS5B抑制剂（BMS-791325）的方案获得了高持久病毒学应答率。
科罗拉多大学奥罗拉丹佛校区的Gregory T. Everson, MD及其同事将32例无肝硬化的1型HCV初治患者随机分为两组给予60 mg NS5A抑制剂DCV一次/天，200mg蛋白酶抑制剂ASV和75mg非核苷类NS5B抑制剂BMS-791325两次/天，组1（N=16）给药24 周，组2（N=16）给药12周。随后又有34例患者随机分为两组给予60 mg DCV一次/天，200mg ASV和150mg BMS-791325两次/天，组3（N=16）给药24周，组4（N=18）给药12周。
除了2例患者，其他所有组的患者都在四周治疗后达到了HCV RNA低于25 IU/ml的水平。92%的患者在四周治疗后实现持续病毒学应答，这一比例在12和24周后达到94%。12和24周治疗后的病毒学应答率无明显差异。
最常见的不良反应（超过10%的患者出现），包括乏力、胃肠道问题和头痛。没有患者出现肝毒性或ALT、AST或胆红素升高到3级或者更高。有两例发生严重不良事件，但都与治疗无关，没有患者因为治疗相关的不良事件中断治疗。
DCV+ASV+BMS-791325方案实现了1型HCV感染初治患者4周、12周和24周高病毒学应答率（通过GT1a和IL28B non-CC检测确定），”研究人员写到，“此方案的耐受性良好，没有明显的安全信号。目前已经在进行进一步研究以更明确此方案的有效性和安全性。”
信息编译自：Interferon-free regimen safe, effective for patients with HCV genotype 1.Healio,October 8, 2013.
原文摘要
Interim Analysis of an Interferon (IFN)- And Ribavirin (RBV)-Free Regimen of Daclatasvir (DCV), Asunaprevir (ASV), and BMS-791325 In Treatment-Naive, Hepatitis C Virus Genotype 1-Infected Patients
Abstract
Background: The IFN- and RBV-free regimen of DCV (NS5A inhibitor), ASV (protease inhibitor) and BMS-791325 (non-nucleoside NS5B inhibitor, 75mg BID) achieved sustained virologic response (SVR4, SVR12) >90% in treatment-naïve, hepatitis C virus (HCV) genotype (GT) 1 patients. We evaluated this regimen using two BMS-791325 doses (75 vs 150 mg BID).
Methods: HCV GT1, treatment-naïve, non-cirrhotic patients (N=32) were randomized 1:1 to DCV 60mg QD, ASV 200mg BID, and BMS-791325 75mg BID for 24 (Group 1) or 12 (Group 2) weeks. Subsequently, 34 additional patients were randomized to DCV, ASV, and BMS-791325 150mg BID for 24 (Group 3) or 12 (Group 4) weeks. The primary end point was HCV RNA <25 IU/mL at 12 weeks post-treatment (SVR12). Interim results are presented.
Results: Patients were mainly GT1a (74%), white (79%), and IL28Bnon-CC (70%). 64/66 patients had HCV RNA <25 IU/mL by Week 4 (Table). There was no difference in virologic response between 12 and 24 weeks of treatment. Overall, patients achieved SVR4 92% (46/50), SVR12 94% (30/32), and SVR24 94% (15/16). No patient discontinued for adverse events (AEs) related to DCV+ASV+BMS-791325. Most common AEs (≥10% total) were headache, asthenia, and gastrointestinal. Two serious AEs were reported, both unrelated to DCV+ASV+BMS-791325. No hepatotoxicity or Grade 3/4 elevations of ALT/AST or bilirubin were reported.
Conclusion: DCV+ASV+BMS-791325 achieved high rates of SVR4, SVR12, and SVR24 in treatment-naive GT1 patients, characterized by GT1a and IL28Bnon-CC. This regimen was well tolerated with no apparent safety signals. Expansion of the current study is underway to better define the efficacy and safety of this regimen.
