title: Ledipasvir-sofosbuvir plus ribavirin for patients with genotype 1 hepatitis C virus previously treated in clinical trials of sofosbuvir regimens.
abstract: Patients who fail to achieve sustained virological response (SVR) after treatment with sofosbuvir (SOF) plus ribavirin (RBV) with or without pegylated interferon (Peg-IFN) do not have established retreatment options. We conducted an open-label trial to assess the efficacy and safety of ledipasvir (LDV)-SOF plus RBV in patients with genotype 1 hepatitis C virus (HCV) who did not achieve SVR after treatment in phase II and III trials of SOF regimens. We enrolled 51 patients at 24 sites in the United States. All patients received the fixed-dose combination tablet of LDV-SOF once-daily plus weight-based RBV (1,000 or 1,200 mg/day) for 12 weeks. The efficacy endpoint was the proportion of patients with SVR 12 weeks after discontinuation of therapy (SVR12). Of the 51 patients enrolled, 25 (49%) had previously received SOF plus Peg-IFN-RBV, 20 (39%) had received SOF-RBV, 5 (10%) had received SOF placebo plus Peg-IFN-RBV, and 1 (2%) received GS-0938 monotherapy. Fourteen (27%) had compensated cirrhosis at baseline, and 47 (92%) had non-CC interleukin-28B genotypes. SVR12 was achieved by 50 of the 51 patients (98%) treated. Among the 45 patients who received SOF in earlier treatment, 44 (98%) achieved SVR12. The only patient who did not achieve SVR12 was a patient with genotype 3a HCV who had been incorrectly genotyped as 1a in the previous study. Given the high rates of SVR12, no differences among patient subgroups were discernible. Of 51 patients, 41 (80%) experienced at least one adverse event (AE), but most events were mild to moderate in severity. The most common AEs were fatigue, headache, and diarrhea. One patient discontinued treatment because of an unrelated AE (bipolar disorder).
  
  
  CONCLUSIONS
  Twelve weeks of LDV-SOF plus RBV was an effective and safe treatment for patients who have not achieved SVR with earlier regimens that included SOF.
authors.affiliation: University of California, San Diego, CA.
authors.forename: David
authors.initials: D
authors.lastname: Wyles
authors.affiliation: Scripps Clinic, La Jolla, CA.
authors.forename: Paul
authors.initials: P
authors.lastname: Pockros
authors.affiliation: University of Florida Health, Gainesville, FL.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Morelli
authors.affiliation: Gastro One, Germantown, TN.
authors.forename: Ziad
authors.initials: Z
authors.lastname: Younes
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: Evguenia
authors.initials: E
authors.lastname: Svarovskaia
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: Jenny C
authors.initials: JC
authors.lastname: Yang
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: Phillip S
authors.initials: PS
authors.lastname: Pang
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: Yanni
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, IL.
authors.forename: Steven
authors.initials: S
authors.lastname: Flamm
authors.affiliation: Texas Liver Institute and the University of Texas Health Science Center, San Antonio, TX.
authors.forename: Eric
authors.initials: E
authors.lastname: Lawitz
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use*; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000627:therapeutic use*; D000069474:Sofosbuvir; D017211:Treatment Failure; D014542:Uridine Monophosphate / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; C000595958:ledipasvir, sofosbuvir drug combination; D012254:Ribavirin; D014542:Uridine Monophosphate; D000069474:Sofosbuvir