Jason Grebely1, Olav Dalgard2, Evan B Cunningham3, Behzad Hajarizadeh3, Graham R Foster4, Philip Bruggmann5, Brian Conway6, Markus Backmund7, Geert Robaeys8, Tracy Swan9, Janaki Amin10, Philippa S Marks3, Sophie Quiene3, Tanya L Applegate3, Martin Weltman11, David Shaw12, Adrian Dunlop13, Margaret Hellard14, Julie Bruneau15, Håvard Midgard16, Stefan Bourgeois17, Cornelia Staehelin18, Gregory J Dore3. 1. The Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia. Electronic address: jgrebely@kirby.unsw.edu.au. 2. Akershus University Hospital, Oslo, Norway; University of Oslo, Oslo, Norway. 3. The Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia. 4. The Liver Unit, Queen Mary University of London, London, United Kingdom. 5. Arud Centres for Addiction Medicine, Zurich, Switzerland. 6. Vancouver Infectious Diseases Center, Vancouver, British Columbia, Canada. 7. Ludwig Maximilians-University Munich, Munich, Germany. 8. Department of Gastroenterology and Hepatology, Ziekenhuis Oost Limburg, Genk, Belgium; Department of Hepatology, UZ Leuven, Leuven, Belgium; Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium. 9. International Network on Hepatitis in Substance Users, New York, NY, United States. 10. The Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia. 11. Nepean Hospital, Sydney, New South Wales, Australia. 12. Royal Adelaide Hospital, Adelaide, South Australia, Australia. 13. School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia. 14. Burnet Institute, Melbourne, Victoria, Australia. 15. Research Center, Centre Hospitalier de l'Universite de Montreal (CRCHUM), Montreal, Quebec, Canada. 16. Department of Infectious Diseases, Akershus University Hospital, Norway; Institute for Clinical Medicine, University of Oslo, Norway; Department of Gastroenterology, Oslo University Hospital, Norway. 17. Stuivenberg ZNA, Antwerp, Belgium. 18. Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.
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.
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: Eshan U Patel; Sunil S Solomon; Allison M Mcfall; Aylur K Srikrishnan; Amrose Pradeep; Paneerselvam Nandagopal; Oliver Laeyendecker; Aaron A R Tobian; David L Thomas; Mark S Sulkowski; M Suresh Kumar; Shruti H Mehta Journal: Int J Drug Policy Date: 2018-04-19
Authors: Andreea A Artenie; Evan B Cunningham; Gregory J Dore; Brian Conway; Olav Dalgard; Jeff Powis; Philip Bruggmann; Margaret Hellard; Curtis Cooper; Philip Read; Jordan J Feld; Behzad Hajarizadeh; Janaki Amin; Karine Lacombe; Catherine Stedman; Alain H Litwin; Pip Marks; Gail V Matthews; Sophie Quiene; Amanda Erratt; Julie Bruneau; Jason Grebely Journal: Clin Infect Dis Date: 2020-05-23 Impact factor: 9.079
Authors: Evan B Cunningham; Behzad Hajarizadeh; Olav Dalgard; Janaki Amin; Margaret Hellard; Graham R Foster; Philip Bruggmann; Brian Conway; Markus Backmund; Geert Robaeys; Tracy Swan; Philippa S Marks; Sophie Quiene; Tanya L Applegate; Martin Weltman; David Shaw; Adrian Dunlop; Julie Bruneau; Håvard Midgard; Stefan Bourgeois; Maria Christine Thurnheer; Gregory J Dore; Jason Grebely Journal: BMC Infect Dis Date: 2017-06-13 Impact factor: 3.090
Authors: Jason Grebely; Phillip Read; Evan B Cunningham; Martin Weltman; Gail V Matthews; Adrian Dunlop; Mark Montebello; Marianne Martinello; Rosie Gilliver; Philippa Marks; Tanya L Applegate; Gregory J Dore Journal: Health Sci Rep Date: 2020-03-15
Authors: Jason Grebely; Jordan J Feld; David Wyles; Mark Sulkowski; Liyun Ni; Joe Llewellyn; Heshaam M Mir; Nika Sajed; Luisa M Stamm; Robert H Hyland; John McNally; Diana M Brainard; Ira Jacobson; Stefan Zeuzem; Marc Bourlière; Graham Foster; Nezam Afdhal; Gregory J Dore Journal: Open Forum Infect Dis Date: 2018-02-09 Impact factor: 3.835