People with hepatitis C virus (HCV) infection who have failed treatment with an all-oral regimen represent a challenging treatment population. The present studies evaluated the safety and efficacy of grazoprevir, ruzasvir, and uprifosbuvir, with or without ribavirin, in participants who had failed an NS5A inhibitor-containing regimen. C-SURGE (PN-3682-021) and C-CREST Part C (PN-3682-011 and -012) were open-label, multicenter studies. Participants who had previously relapsed following an NS5A inhibitor–containing all-oral regimen were retreated with grazoprevir 100 mg, ruzasvir 60 mg, and uprifosbuvir 450 mg alone for 24 weeks or with ribavirin for 16 weeks. The primary efficacy endpoint was sustained virologic response (HCV RNA below the limit of quantitation [<15 IU/mL]) 12 weeks after treatment completion (SVR12). In C-SURGE, SVR12 was achieved by 49/49 (100%) and 43/44 (98%) genotype (GT)1 participants in the 24-week no ribavirin arm and the 16-week plus ribavirin arm (lost to follow-up, n = 1), respectively. In C-CREST Part C, SVR12 was achieved by 23/24 (96%) participants treated for 16 weeks with ribavirin (GT1, 2/2 [100%]; GT2, 13/14 [93%]; GT3, 8/8 [100%]). One participant with GT2 infection discontinued study medication after a single dose of grazoprevir, ruzasvir, and uprifosbuvir plus ribavirin due to serious adverse events of vomiting and tachycardia. The presence of baseline resistance-associated substitutions had no impact on SVR12. No participant who completed treatment in either study experienced virologic failure. Conclusion: Grazoprevir, ruzasvir, and uprifosbuvir, with or without ribavirin, for 16 or 24 weeks was safe and highly effective in participants with HCV infection who had previously failed NS5A inhibitor–containing therapy. (Hepatology 2017;66:1794–1804)

中文翻译：

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NS5A治疗失败后的Grazoprevir，ruzasvir和uprifosbuvir用于丙型肝炎病毒

接受全口服疗法治疗失败的丙型肝炎病毒（HCV）感染者代表了具有挑战性的治疗人群。本研究评估了含或不含利巴韦林的格拉佐普韦，鲁扎斯韦和uprifosbuvir在含NS5A抑制剂治疗方案无效的参与者中的安全性和有效性。C-SURGE（PN-3682-021）和C-CREST Part C（PN-3682-011和-012）是开放标签的多中心研究。先前接受含NS5A抑制剂的全口服方案后复发的参与者分别接受了Grazoprevir 100 mg，ruzasvir 60 mg和uprifosbuvir 450 mg单独治疗24周或利巴韦林治疗16周。主要疗效终点是治疗完成后12周（SVR12）的持续病毒学应答（HCV RNA低于定量限[<15 IU / mL]）。在C-SURGE中 在24周无利巴韦林组和16周加利巴韦林组中，有49/49（100％）和43/44（98％）基因型（GT）1参与者达到SVR12（输往随访，n = 1）。在C-CREST Part C中，接受病毒唑治疗16周的23/24（96％）参与者达到了SVR12（GT1、2 / 2 [100％]，GT2、13 / 14 [93％]，GT3、8 / 8 [100％]）。一名患有GT2感染的参与者由于呕吐和心动过速的严重不良事件，在单剂grazoprevir，ruzasvir和uprifosbuvir联合利巴韦林后停药。基线抗性相关取代的存在对SVR12没有影响。在任何一项研究中均未完成治疗的参与者均未发生病毒学衰竭。13/14 [93％]；GT3，8 / 8 [100％]）。一名患有GT2感染的参与者由于呕吐和心动过速的严重不良事件，在单剂grazoprevir，ruzasvir和uprifosbuvir联合利巴韦林后停药。基线抗性相关取代的存在对SVR12没有影响。在任何一项研究中均未完成治疗的参与者均未发生病毒学衰竭。13/14 [93％]；GT3，8 / 8 [100％]）。一名患有GT2感染的参与者由于呕吐和心动过速的严重不良事件，在单剂grazoprevir，ruzasvir和uprifosbuvir联合利巴韦林后停药。基线抗性相关取代的存在对SVR12没有影响。在任何一项研究中均未完成治疗的参与者均未发生病毒学衰竭。结论： Grazoprevir，ruzasvir和uprifosbuvir联合或不联合利巴韦林治疗16或24周，对于先前曾接受过NS5A抑制剂治疗失败的HCV感染参与者而言，是安全有效的。（肝病学， 2017年； 66：1794–1804）