Effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir in patients with chronic hepatitis C previously treated with DAAs

J Hepatol. 2019 Oct;71(4):666-672. doi: 10.1016/j.jhep.2019.06.002. Epub 2019 Jun 14.


Background & aims: Around 5% of patients with chronic hepatitis C virus (HCV) infection treated with direct-acting antiviral (DAA) agents do not achieve sustained virological response (SVR). The currently approved retreatment regimen for prior DAA failure is a combination of sofosbuvir, velpatasvir, and voxilaprevir (SOF/VEL/VOX), although there is little data on its use in clinical practice. The aim of this study was to analyse the effectiveness and safety of SOF/VEL/VOX in the real-world setting.

Methods: This was a prospective multicentre study assessing the efficacy of retreatment with SOF/VEL/VOX in patients who had experienced a prior DAA treatment failure. The primary endpoint was SVR 12 weeks after the completion of treatment (SVR12). Data on safety and tolerability were also recorded.

Results: A total of 137 patients were included: 75% men, 35% with liver cirrhosis. Most were infected with HCV genotype (GT) 1 or 3. The most common prior DAA combinations were sofosbuvir plus an NS5A inhibitor or ombitasvir/paritaprevir/r+dasabuvir. A total of 136 (99%) patients achieved undetectable HCV RNA at the end of treatment. Overall SVR12 was 95% in the 135 patients reaching this point. SVR12 was lower in patients with cirrhosis (89%, p = 0.05) and those with GT3 infection (80%, p <0.001). Patients with GT3 infection and cirrhosis had the lowest SVR12 rate (69%). Of the patients who did not achieve SVR12, 1 was reinfected and 7 experienced treatment failure (6 GT3, 1 GT1a). The presence of resistance-associated substitutions did not impact SVR12. Adverse effects were mild and non-specific.

Conclusion: Real-world data show that SOF/VEL/VOX is an effective, safe rescue therapy for patients with prior DAA treatment failure despite the presence of resistance-associated substitutions. However, patients with liver cirrhosis infected by GT3 remain the most-difficult-to-treat group.

Lay summary: Treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) for 12 weeks is the current recommendation for the 5% of patients infected with HCV who do not achieve eradication of the virus under treatment with direct-acting antivirals. In a Spanish cohort of 137 patients who failed a previous combination of direct-acting antivirals, a cure rate of 95% was achieved with SOF/VEL/VOX. Genotypic characteristics of the virus (genotype 3) and the presence of cirrhosis were factors that decreased the rate of cure. Treatment with SOF/VEL/VOX is an effective and safe rescue therapy due to its high efficacy and very good safety profile.

Keywords: HCV genotype 3; Hepatitis C; Sofosbuvir; Treatment failures; Velpatasvir; Voxilaprevir.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aminoisobutyric Acids
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Carbamates* / administration & dosage
  • Carbamates* / adverse effects
  • Cyclopropanes
  • Drug Combinations
  • Drug Monitoring / methods
  • Drug Resistance, Viral
  • Female
  • Hepacivirus / genetics
  • Hepatitis C, Chronic* / drug therapy
  • Hepatitis C, Chronic* / epidemiology
  • Hepatitis C, Chronic* / virology
  • Heterocyclic Compounds, 4 or More Rings* / administration & dosage
  • Heterocyclic Compounds, 4 or More Rings* / adverse effects
  • Humans
  • Lactams, Macrocyclic
  • Leucine / analogs & derivatives
  • Liver Cirrhosis / diagnosis*
  • Macrocyclic Compounds* / administration & dosage
  • Macrocyclic Compounds* / adverse effects
  • Male
  • Middle Aged
  • Proline / analogs & derivatives
  • Quinoxalines
  • Sofosbuvir* / administration & dosage
  • Sofosbuvir* / adverse effects
  • Spain / epidemiology
  • Sulfonamides* / administration & dosage
  • Sulfonamides* / adverse effects
  • Sustained Virologic Response
  • Treatment Outcome


  • Aminoisobutyric Acids
  • Antiviral Agents
  • Carbamates
  • Cyclopropanes
  • Drug Combinations
  • Heterocyclic Compounds, 4 or More Rings
  • Lactams, Macrocyclic
  • Macrocyclic Compounds
  • Quinoxalines
  • Sulfonamides
  • voxilaprevir
  • Proline
  • Leucine
  • velpatasvir
  • Sofosbuvir