title: Ledipasvir/sofosbuvir-based treatment of patients with chronic genotype-1 HCV infection and cirrhosis: results from two Phase II studies.
abstract: Ledipasvir/sofosbuvir ± ribavirin administered for 12 weeks to patients with genotype-1 HCV infection and compensated cirrhosis is effective and well-tolerated. The Phase II TRILOGY-1 and TRILOGY-2 studies investigated whether ledipasvir/sofosbuvir plus the non-nucleotide NS5B inhibitor GS-9669 or the NS3/4A protease inhibitor vedroprevir could reduce treatment duration and/or eliminate the need for ribavirin in genotype-1 HCV-infected patients with compensated cirrhosis.
  
  
  
  In TRILOGY-1, 100 cirrhotic patients were randomized (1:1:1) to 8 weeks of ledipasvir/sofosbuvir plus ribavirin, ledipasvir/sofosbuvir plus GS-9669 250 mg or ledipasvir/sofosbuvir plus GS-9669 500 mg. In TRILOGY-2, 46 previously treated cirrhotic patients were randomized (1:1) to 8 weeks of ledipasvir/sofosbuvir plus vedroprevir ± ribavirin. The primary end points were the proportion of patients with sustained virological response 12 weeks after treatment discontinuation (SVR12) and safety.
  
  
  
  In both studies, most patients were male (each 65%) and white (92-96%), infected with HCV genotype-1a (62-70%) and had IL28B non-CC genotypes (82-87%). In total, 37-39% of patients were Hispanic or Latino. SVR12 rates were similar across treatment arms in TRILOGY-1 (82-91%) and TRILOGY-2 (88-95%); no patient had on-treatment virological failure. Two serious adverse events (acute myocardial infarction and cardiomyopathy) were reported in two patients participating in TRILOGY-1, both of whom had pre-existing cardiac conditions. Laboratory abnormalities were infrequent.
  
  
  
  All ledipasvir/sofosbuvir-based regimens were well-tolerated. To shorten therapy and eliminate ribavirin, use of a more potent third agent or a third agent with a different mechanism of action may be required.
authors.affiliation: Texas Liver Institute and the University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Lawitz
authors.affiliation: Texas Liver Institute and the University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Fred
authors.initials: F
authors.lastname: Poordad
authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Hyland
authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
authors.forename: Hadas
authors.initials: H
authors.lastname: Dvory-Sobol
authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Brainard
authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.affiliation: Texas Liver Institute and the University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Julio A
authors.initials: JA
authors.lastname: Gutierrez
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage* / Q000009:adverse effects; D005838:Genotype; D016174:Hepacivirus / Q000145:classification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D000069474:Sofosbuvir / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; C586541:ledipasvir; D000069474:Sofosbuvir