Journal Article

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

Dore, Gregory J., Natha, Macky, Carr, Val, Bronowicki, Jean-Pierre, Mauss, Stefan, Grebely, Jason, Zhu, Yanni, Yang, Junming, Yun, Chohee, Puoti, Massimo, Brown, Ashley, Brainard, Diana M., Wyles, David, Kreter, Bruce

2016

Overview

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 illicity 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. Clinical Trials Registration. ION-1 (NCT01701401); ION-2 (NCT01768286); and ION-3 (NCT01851330).

• Publisher: Oxford University Press
• Subject: Adult / Antiviral Agents - therapeutic use / ARTICLES AND COMMENTARIES / Benzimidazoles - administration & dosage / Benzimidazoles - adverse effects / Benzimidazoles - therapeutic use / Clinical trials / Data Interpretation, Statistical / Drug Therapy, Combination - adverse effects / Drug Users / Enzyme-Linked Immunosorbent Assay / Female / Fluorenes - administration & dosage / Fluorenes - adverse effects / Fluorenes - therapeutic use / Genotype / Genotype & phenotype / Hepacivirus - drug effects / Hepacivirus - genetics / Hepatitis / Hepatitis C virus / Hepatitis C, Chronic - blood / Hepatitis C, Chronic - drug therapy / Hepatitis C, Chronic - genetics / Humans / Male / Middle Aged / Opiate Substitution Treatment / Patient safety / Prescription drugs / Retrospective Studies / Ribavirin - administration & dosage / Ribavirin - adverse effects / Ribavirin - therapeutic use / Safety / Sofosbuvir - administration & dosage / Sofosbuvir - adverse effects / Sofosbuvir - therapeutic use / Substance abuse treatment / Sustained Virologic Response / Viral Load - drug effects