Efficacy and Safety of Sofosbuvir/Velpatasvir/Voxilaprevir for Hepatitis C Virus (HCV) NS5A-Inhibitor Experienced Patients with Difficult to Cure Characteristics

Timothy Papaluca, Stuart K. Roberts, Simone I. Strasser, Katherine A. Stuart, Geoffrey Farrell, Gerry Macquillan, Gregory J. Dore, Amanda J. Wade, Jacob George, Simon Hazeldine, James O'Beirne, Alan Wigg, Leslie Fisher, Bruce McGarity, Rohit Sawhney, Marie Sinclair, James Thomas, Ivan Valiozis, Martin Weltman, Mark WilsonAidan Woodward, Golo Ahlenstiel, Mazhar Haque, Miriam Levy, Emily Prewett, William Sievert, Siddharth Sood, Edmund Tse, Zina Valaydon, Scott Bowden, Mark Douglas, Kate New, Jacinta O'Keefe, Margaret Hellard, Joseph Doyle, Mark Stoove, Alexander J. Thompson

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Background: In clinical trials, hepatitis C virus (HCV) salvage treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) achieved an SVR12 rate of >95% in NS5A-experienced participants. Lower SVR12 rates have been reported in real-world studies, particularly for genotype (GT)3 infection and cirrhosis. We determined the efficacy and safety of SOF/VEL/VOX in a large real-world cohort. Methods: We assessed the efficacy of salvage SOF/VEL/VOX for HCV infection in NS5A-inhibitor experienced participants with cirrhosis and portal hypertension, prior liver transplantation (LT) or severe extra-hepatic manifestations. SOF/VEL/VOX was available via an early access program. The primary outcome was SVR12. Secondary outcome was frequency of adverse events (AE). Findings: Ninety-seven participants were included. Median age was 58, 82% were male, 78% had cirrhosis, most with portal hypertension (61%, n=46/76), and 18% had prior-LT. Of the cirrhotic participants, 96% were Child-Turcotte-Pugh class A, and 4% were class B. Of the 72% with GT3, 76% were also cirrhotic. By intention-to-treat analysis, SVR12 rate was 85% (n=82/97). Per protocol, the SVR12 rate was 90%, including 91% in GT1 (GT1a n=18/18, GT1b n=2/4), 89% in GT3 (n=59/66) and 100% in GT6 (n=3/3). SVR12 in participants with GT3 and cirrhosis was 90%. No predictors of non-SVR12 were identified. There were 4 serious AEs including 1 death and 3 hepatic decompensation events. NS5A resistance-associated substitutions detected at baseline did not affect SVR12. Conclusions: This real-world study confirms high efficacy of SOF/VEL/VOX for the treatment of difficult-to-cure NS5A-inhibitor experienced patients, including those with GT3 and cirrhosis. Treatment was well tolerated in most; however, serious AEs can occur in those with advanced liver disease.

Original languageEnglish
Pages (from-to)E3288-E3295
Number of pages8
JournalClinical Infectious Diseases
Volume73
Issue number9
DOIs
Publication statusPublished - 1 Nov 2021
Externally publishedYes

Keywords

  • cirrhosis
  • genotype 3
  • hepatitis C
  • relapse
  • sofosbuvir/velpatasvir/voxilaprevir

Fingerprint

Dive into the research topics of 'Efficacy and Safety of Sofosbuvir/Velpatasvir/Voxilaprevir for Hepatitis C Virus (HCV) NS5A-Inhibitor Experienced Patients with Difficult to Cure Characteristics'. Together they form a unique fingerprint.

Cite this