Retreatment with elbasvir, grazoprevir, sofosbuvir ± ribavirin is effective for GT3 and GT1/4/6 HCV infection after relapse

Abstract

Introduction: Despite highly effective direct-acting antiviral (DAA) therapies for chronic hepatitis C virus (HCV) infection, some patients experience virological relapse.Salvage regimens should include multiple agents to suppress emergence of resistance-associated substitutions (RAS) and minimise treatment failure. The combination of sofosbuvir (SOF) and elbasvir/grazoprevir (ELB/GZR) ±ribavirin (RBV) is an effective retreatment strategy for HCV genotype (GT)1 and 4 infection. We hypothesised that SOF and ELB/GZR (±RBV) would also be an effective salvage regimen for DAA-experienced GT3 patients. Methods:We evaluated the efficacy and safety of SOF/ELB/GZR ± RBV in DAA-experienced participants with chronic HCV infection who had prior relapse. Participants were treated at four hospitals between December 2016 and March 2018 for either 12-or 16-weeks. The primary endpoint was sustained virological response at week 12 post-treatment (SVR12) using intention-to-treat analysis.Results: There were 40 participants included in the analysis. The mean age was 53 years, 53% had GT3, 33% had GT1 infection and 63% had cirrhosis. Fifty-eight percent were treated for 12 weeks, 42% were treated for 16 weeks and 90% received RBV. The SVR12 rate was 98% overall, 100% in non-GT3 participants and 95% in GT3 participants. One GT3 cirrhotic participant relapsed. ELB/GZR was stopped at week 6 in one GT3 cirrhotic participant who switched to SOF/velpatasvir/RBV for a further 12 weeks and achieved SVR12. RBV dose reduction was required in two participants. Treatment was otherwise well tolerated. Discussion:The combination of SOF/ELB/GZR ± RBV is effective and safe for difficult-to-cure patients who relapse after first-line DAA, including those with cirrhosis and GT3 infection. K E Y W O R D S hepatitis C, resistance-associated substitution, retreatment, salvage, virological relapse S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Papaluca T, Sinclair M, Gow P, et al. Retreatment with elbasvir, grazoprevir, sofosbuvir ± ribavirin is effective for GT3 and GT1/4/6 HCV infection after relapse.

Efficacy and Safety of Glecaprevir/Pibrentasvir in HCV Patients With Previous Direct-Acting Antiviral Therapy Failures: A Meta-Analysis

“…In this meta-analysis, the pooled SVR12, breakthrough, and relapse rates were 96.8% (95%CI: 95.1-98.2), 0.92% (95%CI: 0.08-2.32), and 1.96% (95%CI: 0.78-3.50), respectively. Compared with sofosbuvir/velpatasvir/voxilaprevir (35), and sofosbuvir/elbasvir/grazoprevirs ± ribavirin (36) retreatments, their SVR12 rates were similar. The incidence of failure of GLE/PIB was lower than other regimens, such as sofosbuvir/daclatasvir (5.7%) and sofosbuvir/velpatasvir (3.4%) (37).…”