Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Canada.
University of Ottawa, Ottawa, Ontario, Canada.
Clin Infect Dis. 2021 Jun 1;72(11):e799-e805. doi: 10.1093/cid/ciaa1510.
Despite the current highly effective therapies with direct-acting antiviral agents (DAAs), some patients with chronic hepatitis C virus (HCV) infection still do not achieve sustained virological response (SVR) and require retreatment. Sofosbuvir/velpatasvir/voxilaprevir (SVV) is recommended as the first-line retreatment option for most patients. The aim of this study was to evaluate the efficacy of SVV as salvage therapy after at least one course of DAA.
Data were collected on all HCV-infected patients who failed DAAs and were prescribed SVV from a prospective Canadian registry (CANUHC) including 17 sites across Canada. Factors associated with failure to achieve SVR with SVV therapy and the utility of RAS testing and ribavirin use were evaluated.
A total of 128 patients received SVV after non-SVR with DAA treatment: 80% male, median age 57.5 (31-86), 44% cirrhotic, and 17 patients post liver transplant. First line regimens included: sofosbuvir/velpatasvir (27.3%), sofosbuvir/ledipasvir (26.5%), grazoprevir/elbasvir (12.5%), other (33.5%). Ribavirin was added to SVV in 26 patients due to past sofosbuvir/velpatasvir use (n = 8), complex resistance associated substitution profiles (n = 16) and/or cirrhosis (n = 9). Overall SVR rate was 96% (123/128). Of 35 patients who previously failed sofosbuvir/velpatasvir, 31 (88.5%) achieved SVR compared to 92 of 93 (99%) among those receiving any other regimen (P = .01).
Similar to reports from phase 3 clinical trials, SVV proved highly effective as salvage therapy for patients who failed a previous DAA therapy. Those who failed SVV had at least 2 of the following factors: genotype 3, presence of cirrhosis, past liver transplantation, past exposure to sofosbuvir/velpatasvir and/or complex resistance profiles.
尽管目前有直接作用抗病毒药物（DAA）的高效疗法，一些慢性丙型肝炎病毒（HCV）感染患者仍未达到持续病毒学应答（SVR），需要再次治疗。索磷布韦/维帕他韦/伏西瑞韦（SVV）被推荐为大多数患者的一线再治疗选择。本研究旨在评估 SVV 作为 DAA 治疗失败后至少一个疗程的补救治疗的疗效。
从加拿大一个包括加拿大 17 个地点的前瞻性加拿大登记处（CANUHC）收集所有 HCV 感染患者的数据，这些患者在 DAA 治疗失败后被开具 SVV 处方。评估了与 SVV 治疗失败的 SVR 相关的因素以及 RAS 检测和利巴韦林使用的效用。
共有 128 名患者在 DAA 治疗未达到 SVR 后接受 SVV 治疗：80%为男性，中位年龄 57.5（31-86）岁，44%为肝硬化，17 名患者为肝移植后。一线方案包括：索磷布韦/维帕他韦（27.3%）、索磷布韦/雷迪帕韦（26.5%）、格卡瑞韦/哌仑他韦（12.5%）、其他（33.5%）。由于过去使用过索磷布韦/维帕他韦（n=8）、复杂的耐药相关替代谱（n=16）和/或肝硬化（n=9），26 名患者在 SVV 中添加了利巴韦林。总的 SVR 率为 96%（123/128）。在 35 名先前索磷布韦/维帕他韦治疗失败的患者中，31 名（88.5%）达到 SVR，而在接受任何其他方案的 93 名患者中，有 92 名（99%）达到 SVR（P=0.01）。
与 3 期临床试验报告相似，SVV 作为先前 DAA 治疗失败患者的补救治疗非常有效。SVV 治疗失败的患者至少有以下 2 个因素：基因型 3、肝硬化、既往肝移植、既往接触过索磷布韦/维帕他韦和/或复杂的耐药谱。
