Efficacy of response-guided directly observed pegylated interferon and self-administered ribavirin for people who inject drugs with hepatitis C virus genotype 2/3 infection: The ACTIVATE study.

Abstract

BACKGROUND:

There are few data on treatment for hepatitis C virus (HCV) infection among people with ongoing injecting drug use. This study evaluated the efficacy of response-guided therapy for chronic HCV genotypes 2/3 infection among people with ongoing injecting drug use or receiving opioid substitution therapy (OST). A secondary aim was to identify predictors of HCV treatment response.

METHODS:

ACTIVATE was a multicentre clinical trial recruited between 2012 and 2014. Participants with genotypes 2/3 were treated with directly observed peg-interferon alfa-2b and self-administered ribavirin for 12 (undetectable HCV RNA at week 4) or 24 weeks (detectable HCV RNA at week 4). Participants were recruited from drug treatment clinics, private practices, hospital clinics and community clinics in Australia, Canada, and five countries in Europe. The primary study outcome was sustained virological response (SVR, undetectable HCV RNA >12 weeks post-treatment).

RESULTS:

Among 93 people with ongoing injecting drug use or receiving OST treated for HCV genotype 2/3, 59% had recently (past month) injected drugs, 77% were receiving OST and 56% injected drugs during therapy. Overall SVR was 66% (61/93). SVR was 84% in those with undetectable HCV RNA at week 4 (12 weeks) compared to 38% in those without (24 weeks). In adjusted analysis, cirrhosis vs. no/mild fibrosis [adjusted OR (aOR) 0.33, 95% CI 0.13, 0.86] predicted reduced SVR, while response at week 4 was associated with increased SVR [aOR 8.11, 95% CI 2.73, 24.10]. Recent injecting drug use at baseline or during therapy was not associated with SVR.

CONCLUSION:

This study demonstrates that people with recent injecting drug use or OST with chronic HCV can achieve responses to interferon-based therapy similar to other populations, despite injecting drugs prior to or during therapy. Cirrhosis was predictive of reduced response to HCV therapy, while response at week 4 (despite shortened therapy) was predictive of improved response.

• Authors: Jason Grebely, Olav Dalgard, Evan B Cunningham, Behzad Hajarizadeh, Graham R Foster, Philip Bruggmann, Brian Conway, Markus Backmund, Geert Robaeys, Tracy Swan, Janaki Amin, Philippa S Marks, Sophie Quiene, Tanya L Applegate, Martin Weltman, David Shaw, Adrian Dunlop, Margaret Hellard, Julie Bruneau, Håvard Midgard, Stefan Bourgeois, Cornelia Staehelin, Gregory J Dore, ACTIVATE Study Group
• Journal: The International journal on drug policy (Int J Drug Policy) Vol. 47 Pg. 177-186 (09 2017) ISSN: 1873-4758 [Electronic] Netherlands
• PMID: 28624134 (Publication Type: Clinical Trial, Journal Article, Multicenter Study)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Antiviral Agents
• Interferon alpha-2
• Interferon-alpha
• Recombinant Proteins
• Polyethylene Glycols
• Ribavirin
• peginterferon alfa-2b

Topics

• Adult
• Antiviral Agents (administration & dosage, therapeutic use)
• Drug Therapy, Combination
• Drug Users
• Female
• Genotype
• Hepacivirus (genetics)
• Hepatitis C, Chronic (complications, drug therapy, virology)
• Humans
• Interferon alpha-2
• Interferon-alpha (administration & dosage, therapeutic use)
• Male
• Middle Aged
• Opiate Substitution Treatment
• Polyethylene Glycols (administration & dosage, therapeutic use)
• Recombinant Proteins (administration & dosage, therapeutic use)
• Ribavirin (administration & dosage, therapeutic use)
• Self Administration
• Substance Abuse, Intravenous (complications, virology)
• Viral Load (drug effects)