Retreatment with sofosbuvir, ledipasvir, and add-on ribavirin for patients who failed daclatasvir and asunaprevir combination therapy

J Gastroenterol. 2017 Oct;52(10):1122-1129. doi: 10.1007/s00535-017-1328-z. Epub 2017 Mar 18.


Background: The optimal retreatment regimen for patients with hepatitis C virus (HCV) infection who failed interferon-free, direct-acting antiviral (DAA) therapy is undetermined. In this study, we aimed to evaluate the efficacy and safety of 12-week retreatment with ledipasvir (LDV) and sofosbuvir (SOF) with add-on ribavirin (RBV) for patients who previously failed to respond to HCV-NS5A inhibitor, daclatasvir (DCV), and HCV-NS3 inhibitor, asunaprevir (ASV), therapy.

Methods: This multicenter, prospective study enrolled 15 patients with genotype-1 HCV infection who failed DCV/ASV combination therapy. They were retreated with SOF, LDV, and RBV for 12 weeks and underwent physical examinations and blood tests at baseline, during treatment, and after therapy. At baseline and relapse, NS3/NS5A and NS5B resistance-associated variants (RAVs) were evaluated.

Results: Of the 15 enrolled patients, 73.3% (11/15), 86.7% (13/15), and 0% (0/15) had RAVs in NS3 D168A/V/T/E, NS5A L31I/M/F/V plus Y93H, and NS5B S282T, respectively. Overall, 86.7% (13/15) of patients achieved a sustained viral response, and all patients completed therapy. No patients experienced severe adverse events. Two patients who failed to respond to SOF, LDV, and RBV combination therapy were elderly women, had the IL28B non-TT genotype, and NS5A RAVs in L31I/Y93H or NS5A A92 K at baseline.

Conclusions: This study revealed that SOF, LDV, and RBV combination therapy was effective and well-tolerated for patients with genotype-1 HCV infection who failed DCV and ASV combination therapy. Thus, RBV added to DAA therapy for difficult-to-treat patients might improve treatment outcomes.

Keywords: Daclatasvir; Direct-acting antivirals; Hepatitis C virus; Retreatment; Sofosbuvir.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / adverse effects
  • Benzimidazoles / administration & dosage*
  • Benzimidazoles / adverse effects
  • Drug Therapy, Combination
  • Female
  • Fluorenes / administration & dosage*
  • Fluorenes / adverse effects
  • Genotype
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Imidazoles / administration & dosage
  • Isoquinolines / administration & dosage
  • Male
  • Middle Aged
  • Prospective Studies
  • Retreatment
  • Ribavirin / administration & dosage*
  • Ribavirin / adverse effects
  • Sofosbuvir / administration & dosage*
  • Sofosbuvir / adverse effects
  • Sulfonamides / administration & dosage
  • Treatment Outcome


  • Antiviral Agents
  • Benzimidazoles
  • Fluorenes
  • Imidazoles
  • Isoquinolines
  • Sulfonamides
  • ledipasvir
  • Ribavirin
  • daclatasvir
  • asunaprevir
  • Sofosbuvir