title: Ledipasvir plus sofosbuvir for 12 weeks in patients with hepatitis C genotype 4 infection.
abstract: Genotype 4 hepatitis C virus (HCV) was considered difficult to treat in the era of pegylated interferon-alpha (Peg-IFN-α) and ribavirin regimens. We evaluated the efficacy and safety of therapy with the nonstructural (NS) 5A inhibitor, ledipasvir, combined with the NS5B polymerase inhibitor, sofosbuvir, in patients with HCV genotype 4. In this phase 2, open-label study, 44 patients (22 treatment naïve and 22 treatment experienced) received a fixed-dose combination tablet of 90 mg of ledipasvir and 400 mg of sofosbuvir orally once-daily for 12 weeks. The primary endpoint was the percentage of patients with HCV RNA <15 IU/mL 12 weeks after stopping therapy (SVR12). Among study participants, HCV genotype 4 subtypes were well represented (4a, n = 25; 4d, n = 10; other subtypes, n = 9). Ten patients (23%) had compensated cirrhosis. Of the 22 treatment-experienced patients, 21 (95%) had a non-CC IL-28B genotype. All 44 patients completed the full 12 weeks of dosing. The SVR12 rate was 93% (41 of 44; 95% confidence interval, 81-99). SVR12 rates were similar between treatment-naïve (95%; 21 of 22) and treatment-experienced (91%; 20 of 22) patients. All 3 patients who did not achieve SVR12 had virological relapse within 4 weeks of the end of treatment; all 3 had baseline HCV RNA ≥800,000 IU/mL, a non-CC IL-28B genotype, and pretreatment NS5A resistance-associated variants. None of the patients who relapsed had cirrhosis. The most common adverse events were asthenia, headache, and fatigue. No patients experienced a serious adverse event.
  
  
  
  The all-oral regimen of ledipasvir and sofosbuvir is an effective and safe treatment for a wide range of HCV 4 subtypes in both treatment-naïve and -experienced patients, including those with compensated cirrhosis. (EudraCT number: 2013-003978-27; Clinicaltrials.gov NCT02081079) (Hepatology 2016;64:1049-1056).
authors.affiliation: Department of Hepatology and Gastroenterology, Centre Hospitalier Universitaire Estaing, Université d'Auvergne, UMR CNRS 6284, Clermont-Ferrand, France. aabergel@chu-clermontferrand.fr.
authors.forename: Armand
authors.initials: A
authors.lastname: Abergel
authors.affiliation: Department of Hepatology and Gastroenterology, Centre Hospitalier Universitaire Purpan, Toulouse, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Metivier
authors.affiliation: Centre Hépato-Biliaire, Hôpital Paul Brousse, Assistance Publique-Hôpitaux de Paris, UMR-S 1193, Université Paris-Sud, INSERM U785, Villejuif, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.affiliation: Gilead Sciences, Inc, Foster City, CA.
authors.forename: Deyuan
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Gilead Sciences, Inc, Foster City, CA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Kersey
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: Evguenia
authors.initials: E
authors.lastname: Svarovskaia
authors.affiliation: Gilead Sciences, Inc, Foster City, CA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Knox
authors.affiliation: Department of Hepatology and Gastroenterology, Centre Hospitalier Universitaire Limoges, U850 INSERM, Université de Limoges, Limoges, France.
authors.forename: Veronique
authors.initials: V
authors.lastname: Loustaud-Ratti
authors.affiliation: Department of Hepatology, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Université Paris-Diderot and INSERM UMR1149, Clichy, France.
authors.forename: Tarik
authors.initials: T
authors.lastname: Asselah
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D001562:Benzimidazoles / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage*; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069474:Sofosbuvir / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; C586541:ledipasvir; D000069474:Sofosbuvir