Elsevier

International Journal of Drug Policy

Volume 47, September 2017, Pages 230-238
International Journal of Drug Policy

Changes in risk behaviours during and following treatment for hepatitis C virus infection among people who inject drugs: The ACTIVATE study

https://doi.org/10.1016/j.drugpo.2017.05.040Get rights and content

Abstract

Background

The risk of hepatitis C virus (HCV) reinfection due to continued injecting risk behaviours might remain a barrier to HCV treatment among people who inject drugs. We aimed to evaluate changes in risk behaviours during and following HCV treatment among people with ongoing injecting drug use or receiving opioid substitution treatment (OST).

Methods

ACTIVATE was an international multicentre clinical trial conducted between 2012 and 2014. Participants with HCV genotypes 2/3 infection were treated with peg-interferon/ribavirin for 12 or 24 weeks and completed a self-administered behavioural questionnaire at each study visit. The impact of time in treatment and follow-up on longitudinally measured recent (past month) behavioural outcomes was evaluated using generalized estimating equations.

Results

Among 93 enrolled participants (83% male, median age 41 years), 55 (59%) had injected in the past month. Any injecting drug use decreased during HCV treatment and follow-up (OR 0.89 per incremental study visit; 95% CI 0.83–0.95). No significant changes were found in ≥daily injecting (OR 0.98; 95% CI 0.89–1.07), use of non-sterile needles (OR 0.94; 95% CI 0.79–1.12), sharing of injecting paraphernalia (OR 0.87; 95% CI 0.70–1.07) or non-injecting drug use (OR 1.01; 95% CI 0.92–1.10). Hazardous alcohol use decreased throughout (OR 0.56; 95% CI 0.40–0.77) and OST increased between enrolment and end of treatment (OR 1.48; 95% CI 1.07–2.04).

Conclusions

Recent injecting drug use and hazardous alcohol use decreased, while OST increased during and following HCV treatment among participants with ongoing injecting drug use. These findings support further expansion of HCV care among PWID.

Introduction

The burden of hepatitis C virus (HCV) infection among people who inject drugs (PWID) is increasing, particularly among older individuals (Hajarizadeh, Grebely, & Dore, 2013; Kielland, Skaug, Amundsen, & Dalgard, 2013). Although HCV treatment in PWID has shown good outcomes (Aspinall et al., 2013; Hellard, Sacks-Davis, & Gold, 2009) and is recommended by international guidelines (AASLD-IDSA, 2015; EASL, 2017; Grebely et al., 2015; WHO, 2016), access to treatment has been limited (Alavi et al., 2014; Grebely et al., 2009; Iversen et al., 2014) due to multiple barriers to care (Bruggmann, 2012; McGowan & Fried, 2012). With increasing use of tolerable and highly effective interferon (IFN)-free directly acting antiviral (DAA) regimens, HCV treatment for PWID should become more feasible.

The potential risk of HCV reinfection due to continued injecting risk behaviours is of considerable interest as it might compromise both individual- and population-level treatment benefits among PWID (Midgard et al., 2016). Concern has also been raised that side effects of IFN-based treatment could mimic opioid withdrawal symptoms and hence promote injecting risk behaviours (Myles, Mugford, Zhao, Krahn, & Peizhong, 2011; Schaefer, Sarkar, & Diez-Quevedo, 2013). On the other hand, receiving HCV-related information and counselling through interaction with health care providers could enhance patient empowerment and lead to favourable behavioural change (Bruneau et al., 2014; MacArthur et al., 2014). A better understanding of patterns of drug use and risk behaviours, and the potential impact of HCV treatment, is needed as we enter the DAA treatment era.

There is, however, limited data on the relationship between HCV treatment and risk behaviours. Some earlier studies of HCV treatment among people receiving opioid substitution treatment (OST) have shown that drug use did not increase during treatment (Mauss, Berger, Goelz, Jacob, & Schmutz, 2004; Sasadeusz et al., 2011). In a study among PWID with recent HCV infection (Alavi et al., 2015), HCV treatment was not associated with increased injecting drug use during follow-up, but was associated with decreased sharing of ancillary injecting equipment. In a recent study of IFN-free HCV treatment for persons receiving OST (Dore et al., 2016), illicit drug use remained unchanged throughout treatment.

The ACTIVATE (A Collaborative Trial in Injectors of indiViduAlized Treatment for genotypE 2/3) study was designed to investigate IFN-based HCV treatment among people with ongoing injection drug use or receiving OST (Grebely et al., 2017). The primary aim of the present study was to evaluate changes in recent injecting drug use during and following HCV treatment among participants enrolled in the ACTIVATE study. The secondary aims were to assess changes in recent injecting risk behaviours, non-injecting drug use, hazardous alcohol use and OST.

Section snippets

Study participants

From May 11 2012, to September 30 2014, participants were enrolled at 17 sites in Australia (n = 5), Canada (n = 3), Switzerland (n = 3), Belgium (n = 2), Germany (n = 1), Norway (n = 2), and the United Kingdom (n = 1). Study recruitment was conducted through a network of hospital clinics (n = 9), drug and alcohol clinics (n = 3), office-based practices (n = 2) and community clinics (n = 3). Harm reduction services (i.e. OST and needle and syringe provision) were available for participants across all study sites.

Characteristics of study participants

Characteristics at enrolment for the 93 participants enrolled are shown in Table 1. The median age was 41 years (IQR 35–50 years), 83% were male, 69% had high school or higher education, 15% had part- or full-time employment and 76% had stable housing. Among 93 participants, 55 (59%) had injected in the past month prior to enrolment, and among those, 27% reported ≥daily injecting, 13% had used non-sterile needles and 15% had shared injection paraphernalia. Eighty-seven percent of participants

Discussion

This international multicentre study evaluated changes in risk behaviours longitudinally during and following HCV treatment among PWID with ongoing injecting drug use or receiving OST. Any injecting drug use and hazardous alcohol use decreased significantly throughout treatment and follow-up, whereas ≥daily injecting, use of non-sterile needles, sharing of injecting paraphernalia, and non-injecting drug use remained stable. OST increased during treatment, but this change did not endure towards

Funding

The ACTIVATE study was supported in part by a research grant from the Investigator Initiated Studies Program of Merck Sharp & Dohme Corp. The Opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme Corp. The Kirby Institute is funded by the Australian Government Department of Health. The views expressed in this publication do not necessarily represent the position of the Australian Government. Håvard Midgard is supported by

Conflicts of interest

HM: Consultant/advisor for Gilead Sciences and Abbvie; sponsored lectures for Roche, Medivir, Gilead Sciences, Merck Sharp & Dohme and AbbVie. BC: Consultant/advisor and research grants from AbbVie, Cepheid, Gilead and Merck Sharp & Dohme. PB: Consultant/advisor and research grants from Abbvie, Bristol Myers Squibb, Gilead, Janssen and Merck. GRF: consultant/advisor and research grants from Abbvie, Bristol Myers Squibb, Gilead Sciences, Janssen, Roche and Merck/MSD. GR: Research grants from

Acknowledgements

The authors would like to thank the study participants for their contribution to the research, as well as current and past researchers and staff. They would like to acknowledge members of the study group:

Protocol Steering Committee—Gregory Dore (Chair, UNSW Sydney), Jason Grebely (UNSW Sydney), Philip Bruggmann (Arud Centres for Addiction Medicine, Zurich, Switzerland), Philippa Marks (UNSW Sydney), Brian Conway (Vancouver Infectious Diseases Center, Vancouver, Canada), Geert Robaeys

References (36)

  • AASLD-IDSA

    AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus

    (2015)
  • M. Alavi et al.

    Continued low uptake of treatment for hepatitis C virus infection in a large community-based cohort of inner city residents

    Liver International

    (2014)
  • E.J. Aspinall et al.

    Treatment of hepatitis C virus infection among people who are actively injecting drugs: A systematic review and meta-analysis

    Clinical Infectious Diseases

    (2013)
  • P. Bruggmann

    Accessing Hepatitis C patients who are difficult to reach: It is time to overcome barriers

    Journal of Viral Hepatitis

    (2012)
  • J. Bruneau et al.

    Sustained drug use changes after hepatitis C screening and counseling among recently infected persons who inject drugs: A longitudinal study

    Clinical Infectious Diseases

    (2014)
  • K. Bush et al.

    The AUDIT alcohol consumption questions (AUDIT-C): An effective brief screening test for problem drinking. Ambulatory Care Quality Improvement Project (ACQUIP). Alcohol use disorders identification test

    Archives of Internal Medicine

    (1998)
  • V.J. Desmet et al.

    Classification of chronic hepatitis: Diagnosis grading and staging

    Hepatology

    (1994)
  • G.J. Dore et al.

    Elbasvir–Grazoprevir to treat hepatitis C virus infection in persons receiving opioid agonist therapy: a randomized trial

    Annals of Internal Medicine

    (2016)
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    1

    Contributed equally.

    2

    Membership of the ACTIVATE Study Group is provided in the Acknowledgments.

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