Hepatology Unit, University Hospital, CHU Bordeaux, Pessac.
INSERM, Université Bordeaux, UMR1053 Bordeaux Research in Translational Oncology, BaRITOn.
Clin Infect Dis. 2018 Mar 19;66(7):1013-1018. doi: 10.1093/cid/cix916.
Failure to achieve sustained virological response (SVR) with hepatitis C virus (HCV) direct-acting antiviral (DAA)-based regimens is commonly associated with emergence of resistance-associated substitutions (RASs). Retreatment of patients who failed prior DAAs remains challenging. The aim of this prospective and randomized study was to evaluate the efficacy (primary endpoint: SVR 12 weeks after end of treatment [SVR12]) and safety of sofosbuvir + grazoprevir/elbasvir + ribavirin for 16 or 24 weeks in patients who had failed to achieve SVR on previous NS5A- or NS3-based therapy and with evidence of RASs at failure.
Patients were chronically infected with HCV genotype 1 or 4. Most of them had advanced fibrosis or compensated cirrhosis (liver stiffness 5.8-48.8 kPa).
All patients achieved HCV RNA below the lower limit of quantification (either target detected [unquantifiable] or target not detected) during treatment. SVR12 was achieved by 25 of 26 patients. The only patient who did not reach SVR was a patient who died, but HCV RNA was negative at this time (5 weeks after stopping treatment). No patient discontinued treatment because of adverse events or virological failure. Globally, treatment was well tolerated.
Our findings support the concept of retreating with sofosbuvir + grazoprevir/elbasvir + ribavirin, for 16 weeks, genotype 1 or 4 DAA-experienced patients with proven NS5A or NS3 RASs.
NCT02647632.
慢性丙型肝炎病毒（HCV）直接作用抗病毒（DAA）方案治疗未能持续病毒学应答（SVR）通常与耐药相关替代（RAS）的出现有关。先前 DAA 治疗失败患者的再治疗仍然具有挑战性。本前瞻性、随机研究的目的是评估索磷布韦+格卡瑞韦/哌仑他韦+利巴韦林 16 或 24 周治疗方案在先前 NS5A 或 NS3 为基础的治疗失败且存在 RASs 的患者中的疗效（主要终点：治疗结束后 12 周的 SVR12）和安全性。
患者慢性 HCV 基因型 1 或 4 感染。大多数患者存在晚期纤维化或代偿性肝硬化（肝硬度 5.8-48.8kPa）。
所有患者在治疗期间均实现了 HCV RNA 低于定量下限（检测到靶标[不可量化]或未检测到靶标）。26 例患者中有 25 例达到 SVR12。唯一未达到 SVR12 的患者是死亡患者，但此时 HCV RNA 为阴性（治疗停止后 5 周）。没有患者因不良反应或病毒学失败而停止治疗。总体而言，治疗耐受性良好。
我们的研究结果支持对证实存在 NS5A 或 NS3 RASs 的基因型 1 或 4 DAA 经验丰富的患者，采用索磷布韦+格卡瑞韦/哌仑他韦+利巴韦林进行 16 周治疗的理念。
NCT02647632。
