Sofosbuvir/Velpatasvir/Voxilaprevir Versus Sofosbuvir/Velpatasvir Plus Ribavirin in Patients With Hepatitis C Virus Genotype 3b and Compensated Cirrhosis: A Multicentre Randomized Controlled Trial

J Med Virol. 2025 Nov;97(11):e70709. doi: 10.1002/jmv.70709.

Abstract

Treatment recommendations for patients with hepatitis C virus (HCV) genotype (GT) 3b infection and cirrhosis remain unclear. This multicentre randomized controlled trial evaluated the efficacy of 12-week treatment with sofosbuvir/velpatasvir plus ribavirin (arm A) versus sofosbuvir/velpatasvir/voxilaprevir (arm B) in direct-acting antiviral (DAA)-naïve patients with HCV GT3b with compensated cirrhosis. Patients with HCV GT3b infection and compensated cirrhosis from eight sites in China were randomised 1:1 into arms A (n = 30) or B (n = 31) for 12 weeks of treatment and 12 weeks of follow-up. The primary endpoint was sustained virological response (SVR) at week 12 Posttreatment. Baseline characteristics were balanced across both arms. Seven participants did not complete treatment (arm A, 4; arm B, 3). The SVR proportions were lower in arm A (70%, 95% CI 52-83) than in arm B (90%, 95% CI 75-97) (p = 0.046) in the intention-to-treat analysis. Per-protocol analysis showed SVR proportions of 81% (95% CI, 62-91) in arm A and 100% (95% CI, 88-100) in arm B (p = 0.021). All five virological failures were in arm A. 98.3% (60/61) of the participants had baseline dual resistance-associated substitutions (RASs) A30K and L31M and all had dual RASs at relapse, with several new RASs emerging. Both regimens were well tolerated, with one serious adverse event in arm A. Compared to sofosbuvir/velpatasvir plus ribavirin, 12 weeks of sofosbuvir/velpatasvir/voxilaprevir treatment suggests a higher SVR proportion in DAA-naïve patients with HCV GT3b with compensated cirrhosis. Clinical Trial Number: NCT05467826.

Keywords: direct‐acting antivirals (DAA); genotype 3b; hepatitis C virus (HCV); resistance‐associated substitutions (RASs); sofosbuvir/velpatasvir; sofosbuvir/velpatasvir/voxilaprevir.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aminoisobutyric Acids
  • Antiviral Agents* / therapeutic use
  • Benzimidazoles
  • Benzopyrans
  • Carbamates* / therapeutic use
  • China
  • Cyclopropanes
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus* / classification
  • Hepacivirus* / drug effects
  • Hepacivirus* / genetics
  • Hepatitis C, Chronic* / complications
  • Hepatitis C, Chronic* / drug therapy
  • Hepatitis C, Chronic* / virology
  • Heterocyclic Compounds, 4 or More Rings* / therapeutic use
  • Humans
  • Lactams, Macrocyclic
  • Leucine / analogs & derivatives
  • Liver Cirrhosis* / drug therapy
  • Liver Cirrhosis* / virology
  • Macrocyclic Compounds* / therapeutic use
  • Male
  • Middle Aged
  • Proline / analogs & derivatives
  • Quinoxalines
  • Ribavirin / therapeutic use
  • Sofosbuvir / therapeutic use
  • Sulfonamides / therapeutic use
  • Sustained Virologic Response
  • Treatment Outcome
  • Valine / analogs & derivatives

Substances

  • Aminoisobutyric Acids
  • Antiviral Agents
  • Carbamates
  • Cyclopropanes
  • Heterocyclic Compounds, 4 or More Rings
  • Lactams, Macrocyclic
  • Leucine
  • Macrocyclic Compounds
  • Proline
  • Ribavirin
  • Sofosbuvir
  • Sulfonamides
  • Valine
  • velpatasvir
  • voxilaprevir
  • Benzimidazoles
  • Benzopyrans
  • Quinoxalines

Associated data

  • ClinicalTrials.gov/NCT05467826