title: Efficacy and Safety of Ledipasvir/Sofosbuvir With and Without Ribavirin in Patients With Chronic HCV Genotype 1 Infection Receiving Opioid Substitution Therapy: Analysis of Phase 3 ION Trials.
abstract: BACKGROUND
  Interferon-based hepatitis C virus (HCV) therapy is safe and effective among people receiving opioid substitution therapy (OST), but treatment uptake remains low. Our aim was to evaluate the impact of OST and drug use during therapy on completion, adherence, sustained virologic response (SVR12), and safety of ledipasvir/sofosbuvir ± ribavirin.
  
  
  METHODS
  The phase 3 ION studies evaluated a fixed-dose combination of ledipasvir/sofosbuvir ± ribavirin administered for 8, 12, or 24 weeks in patients with chronic HCV genotype 1. People with clinically significant drug use (prior 12 months) or noncannabinoids detected at screening by urine drug tests (not explained by prescriptions) were ineligible. Stored samples were available from ION-1 for retrospective testing for illicit drugs by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Among 1952 patients enrolled in the ION studies, 4% (n = 70) were receiving OST. Among those receiving (n = 70) and not receiving OST (n = 1882), there was no difference in treatment completion (97% vs 98%; P = .40), ≥80% adherence (93% vs 92%; P = 1.00), SVR12 (94% vs 97%; P = .28), and serious adverse events (4% vs 3%; P = .43), respectively. Among participants in the ION-1 trial, 23% (n = 196) used illicit drugs during therapy (15% cannabinoids alone; 8% other illicit drugs ± cannabinoids). There was no difference in treatment completion, ≥80% adherence, SVR12, or serious AEs in those with no drug use during treatment compared with those who used cannabinoids and/or other illicit drugs. No cases of HCV reinfection were observed in the 24 weeks following treatment.
  
  
  CONCLUSIONS
  OST and drug use during HCV therapy did not impact treatment completion, adherence, SVR12, or safety.
  
  
  BACKGROUND
  ION-1 (NCT01701401); ION-2 (NCT01768286); and ION-3 (NCT01851330).
authors.affiliation: The Kirby Institute, UNSW Australia, Sydney.
authors.forename: Jason
authors.initials: J
authors.lastname: Grebely
authors.affiliation: Center for HIV and Hepatogastroenterology, Düsseldorf, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Mauss
authors.affiliation: Liver Unit, Department of Medicine, St Mary's Hospital, London, United Kingdom.
authors.forename: Ashley
authors.initials: A
authors.lastname: Brown
authors.affiliation: INSERM U954, Universitary Hospital of Nancy, University of Lorraine, Vandoeuvre-les-Nancy, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bronowicki
authors.affiliation: Azienda Ospedaliera Ospedale Niguarda Ca' Granda, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Puoti
authors.affiliation: Division of Infectious Diseases, University of California, San Diego.
authors.forename: David
authors.initials: D
authors.lastname: Wyles
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Macky
authors.initials: M
authors.lastname: Natha
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Yanni
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Junming
authors.initials: J
authors.lastname: Yang
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Bruce
authors.initials: B
authors.lastname: Kreter
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Brainard
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Chohee
authors.initials: C
authors.lastname: Yun
authors.affiliation: Gilead Sciences, Stockley Park, United Kingdom.
authors.forename: Val
authors.initials: V
authors.lastname: Carr
authors.affiliation: The Kirby Institute, UNSW Australia, Sydney.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003627:Data Interpretation, Statistical; D004359:Drug Therapy, Combination / Q000009:adverse effects; D055030:Drug Users; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D058850:Opiate Substitution Treatment; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069474:Sofosbuvir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000072230:Sustained Virologic Response; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; C586541:ledipasvir; D012254:Ribavirin; D000069474:Sofosbuvir
keywords: DAA; PWID; drug use; hepatitis C virus; opioid substitution therapy