Adherence to response-guided pegylated interferon and ribavirin for people who inject drugs with hepatitis C virus genotype 2/3 infection: the ACTIVATE study

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, ACTIVATE Study Group, 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, ACTIVATE Study Group

Abstract

Background: The aims of this analysis were to investigate treatment completion and adherence among people with ongoing injecting drug use or receiving opioid substitution therapy (OST) in a study of response-guided therapy for chronic HCV genotypes 2/3 infection.

Methods: ACTIVATE was a multicenter clinical trial recruited between 2012 and 2014. Participants with genotypes 2/3 were treated with directly observed peg-interferon alfa-2b (PEG-IFN) and self-administered ribavirin for 12 (undetectable HCV RNA at week 4) or 24 weeks (detectable HCV RNA at week 4). Outcomes included treatment completion, PEG-IFN adherence, ribavirin adherence, and sustained virological response (SVR, undetectable HCV RNA >12 weeks post-treatment).

Results: Among 93 people treated, 59% had recently injected drugs (past month), 77% were receiving OST and 56% injected drugs during therapy. Overall, 76% completed treatment. Mean on-treatment adherence to PEG-IFN and ribavirin were 98.2% and 94.6%. Overall, 6% of participants missed >1 dose of PEG-IFN and 31% took <95% of their prescribed ribavirin., Higher treatment completion was observed among those receiving 12 vs. 24 weeks of treatment (97% vs. 46%, P < 0.001) while the proportion of participants with 95% on-treatment ribavirin adherence was similar between groups (67% vs. 72%, P = 0.664). Receiving 12 weeks of therapy was independently associated with treatment completion. No factors were associated with 95% RBV adherence. Neither recent injecting drug use at baseline nor during therapy was associated with treatment completion or adherence to ribavirin. In adjusted analysis, treatment completion was associated with SVR (aOR 23.9, 95% CI 2.9-193.8).

Conclusions: This study demonstrated a high adherence to directly observed PEG-IFN and self-administered ribavirin among people with ongoing injecting drug use or receiving OST. These data also suggest that shortening therapy from 24 to 12 weeks can lead to improved treatment completion. Treatment completion was associated with improved response to therapy. ACTIVATE trial registration number: NCT01364090 - May 31, 2011.

Keywords: Adherence; Hepatitis C; Injection drug use; PWID; Treatment.

Figures

Fig. 1
Fig. 1
Weekly PEG-IFN adherence among HCV genotype 2/3 participants on shortened (12 weeks; n = 61; panel a) and standard therapy (24 weeks; n = 26; panel b). Each row represents a study participant. Dark green boxes represent a full prescribed dose was received, light green boxes represent an adjusted dose was received, and white boxes represent a missed dose
Fig. 2
Fig. 2
Time to treatment discontinuation among study participants who were in the shortened (12 week; n = 61) and standard (24 week; n = 26) arm
Fig. 3
Fig. 3
Four-weekly RBV adherence among HCV genotype 2/3 participants on shortened (12 weeks; n = 61; panel a) and standard therapy (24 weeks; n = 26; panel b). Each row represents a study participant. Colours represent each participant’s RBV adherence during each four-week period with dark green representing 100% adherence and red representing 0% adherence. White represents discontinuation before completion of the corresponding time-point while black represents missing data for both retuned pill counts and patient reported adherence before treatment discontinuation

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