PMID- 30735896 OWN - NLM STAT- MEDLINE DCOM- 20200207 LR - 20200207 IS - 1873-4758 (Electronic) IS - 0955-3959 (Linking) VI - 66 DP - 2019 Apr TI - Safety and efficacy of glecaprevir/pibrentasvir in patients with chronic hepatitis C genotypes 1-6 receiving opioid substitution therapy. PG - 73-79 LID - S0955-3959(19)30019-2 [pii] LID - 10.1016/j.drugpo.2019.01.011 [doi] AB - BACKGROUND: International guidelines recommend treatment of hepatitis C virus (HCV) infection in people who inject drugs (PWID), including those on opioid substitution therapy (OST). The pangenotypic combination of glecaprevir and pibrentasvir has shown high sustained virologic response at post-treatment Week 12 (SVR12) in clinical trials. Herein, we evaluate the safety and efficacy of glecaprevir/pibrentasvir in patients receiving OST. METHODS: Pooled data from patients with HCV genotypes 1-6 who were treated with glecaprevir/pibrentasvir for 8, 12, or 16 weeks in eight Phase 2 and 3 trials were categorized by use of OST. Treatment completion, treatment adherence, SVR12, adverse events (AEs), and laboratory abnormalities were evaluated for patients receiving and not receiving OST. RESULTS: Among 2256 patients, 157 (7%) were receiving OST. Compared with patients not receiving OST, OST patients were younger (mean age, 46.8 vs 52.8 years), male (69% vs 54%), white (93% vs 80%), HCV treatment-naive (86% vs 72%), had HCV genotype 3 (60% vs 26%), and had a history of depression or bipolar disorder (43% vs 19%). Most patients completed (OST: 98% [n/N = 154/157]; non-OST: 99% [n/N = 2070/2099]) and were adherent (received >/=90% of study drug doses) to glecaprevir/pibrentasvir treatment (OST: 98% [n/N = 121/123]; non-OST: 99% [n/N = 1884/1905] among patients with available data). In the intention-to-treat population, SVR12 rates in OST and non-OST patients were 96.2% (n/N = 151/157; 95% CI 93.2-99.2) and 97.9% (n/N = 2055/2099; 95% CI 97.3-98.5), respectively. For OST patients, reasons for nonresponse included virologic relapse (<1%; n = 1), premature study drug discontinuation (<1%; n = 1), and loss to follow-up (3%; n = 4). AEs occurring in >/=10% of OST patients were headache, fatigue, and nausea. Drug-related serious AEs, AEs leading to study drug discontinuation, and Grade 3 or higher laboratory abnormalities were infrequent in both groups (<1%). No HCV reinfections occurred through post-treatment Week 12. CONCLUSION: Glecaprevir/pibrentasvir is highly efficacious and well tolerated in HCV-infected patients receiving OST. CI - Copyright (c) 2019 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Grebely, Jason AU - Grebely J AD - The Kirby Institute, UNSW Sydney, Sydney, Australia. Electronic address: jgrebely@kirby.unsw.edu.au. FAU - Dore, Gregory J AU - Dore GJ AD - The Kirby Institute, UNSW Sydney, Sydney, Australia. FAU - Alami, Negar N AU - Alami NN AD - AbbVie, North Chicago, IL, USA. FAU - Conway, Brian AU - Conway B AD - Vancouver Infectious Diseases Centre, Vancouver, Canada. FAU - Dillon, John F AU - Dillon JF AD - Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, Dundee, UK. FAU - Gschwantler, Michael AU - Gschwantler M AD - Department of Internal Medicine IV, Wilhelminenspital, Vienna, Austria; Sigmund Freud University, Vienna, Austria. FAU - Felizarta, Franco AU - Felizarta F AD - Private Practice, Bakersfield, CA, USA. FAU - Hezode, Christophe AU - Hezode C AD - Department of Hepatology, Hopital Henri Mondor, Universite Paris-Est, Paris, France. FAU - Tomasiewicz, Krzysztof AU - Tomasiewicz K AD - Department of Infectious Diseases and Hepatology, Medical University of Lublin, Lublin, Poland. FAU - Fredrick, Linda M AU - Fredrick LM AD - AbbVie, North Chicago, IL, USA. FAU - Dumas, Emily O AU - Dumas EO AD - AbbVie, North Chicago, IL, USA. FAU - Mensa, Federico J AU - Mensa FJ AD - AbbVie, North Chicago, IL, USA. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't DEP - 20190206 PL - Netherlands TA - Int J Drug Policy JT - The International journal on drug policy JID - 9014759 RN - 0 (Antiviral Agents) RN - 0 (Benzimidazoles) RN - 0 (Drug Combinations) RN - 0 (Pyrrolidines) RN - 0 (Quinoxalines) RN - 0 (Sulfonamides) RN - 0 (glecaprevir and pibrentasvir) SB - IM MH - Adult MH - Antiviral Agents/*administration & dosage/adverse effects MH - Benzimidazoles/*administration & dosage/adverse effects MH - Clinical Trials, Phase II as Topic MH - Clinical Trials, Phase III as Topic MH - Drug Combinations MH - Female MH - Genotype MH - Hepacivirus/genetics MH - Hepatitis C, Chronic/*drug therapy MH - Humans MH - Male MH - Middle Aged MH - Opiate Substitution Treatment/*methods MH - Pyrrolidines/*administration & dosage/adverse effects MH - Quinoxalines/*administration & dosage/adverse effects MH - Substance Abuse, Intravenous/rehabilitation MH - Sulfonamides/*administration & dosage/adverse effects OTO - NOTNLM OT - Glecaprevir/pibrentasvir OT - Hepatitis C virus OT - Opioid substitution therapy OT - People who inject drugs EDAT- 2019/02/09 06:00 MHDA- 2020/02/08 06:00 CRDT- 2019/02/09 06:00 PHST- 2018/06/19 00:00 [received] PHST- 2018/12/13 00:00 [revised] PHST- 2019/01/07 00:00 [accepted] PHST- 2019/02/09 06:00 [pubmed] PHST- 2020/02/08 06:00 [medline] PHST- 2019/02/09 06:00 [entrez] AID - S0955-3959(19)30019-2 [pii] AID - 10.1016/j.drugpo.2019.01.011 [doi] PST - ppublish SO - Int J Drug Policy. 2019 Apr;66:73-79. doi: 10.1016/j.drugpo.2019.01.011. Epub 2019 Feb 6.