Commentary
Research priorities to achieve universal access to hepatitis C prevention, management and direct-acting antiviral treatment among people who inject drugs

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Abstract

Globally, it is estimated that 71.1 million people have chronic hepatitis C virus (HCV) infection, including an estimated 7.5 million people who have recently injected drugs (PWID). There is an additional large, but unquantified, burden among those PWID who have ceased injecting. The incidence of HCV infection among current PWID also remains high in many settings. Morbidity and mortality due to liver disease among PWID with HCV infection continues to increase, despite the advent of well-tolerated, simple interferon-free direct-acting antiviral (DAA) HCV regimens with cure rates >95%. As a result of this important clinical breakthrough, there is potential to reverse the rising burden of advanced liver disease with increased treatment and strive for HCV elimination among PWID. Unfortunately, there are many gaps in knowledge that represent barriers to effective prevention and management of HCV among PWID. The Kirby Institute, UNSW Sydney and the International Network on Hepatitis in Substance Users (INHSU) established an expert round table panel to assess current research gaps and establish future research priorities for the prevention and management of HCV among PWID. This round table consisted of a one-day workshop held on 6 September, 2016, in Oslo, Norway, prior to the International Symposium on Hepatitis in Substance Users (INHSU 2016). International experts in drug and alcohol, infectious diseases, and hepatology were brought together to discuss the available scientific evidence, gaps in research, and develop research priorities. Topics for discussion included the epidemiology of injecting drug use, HCV, and HIV among PWID, HCV prevention, HCV testing, linkage to HCV care and treatment, DAA treatment for HCV infection, and reinfection following successful treatment. This paper highlights the outcomes of the roundtable discussion focused on future research priorities for enhancing HCV prevention, testing, linkage to care and DAA treatment for PWID as we strive for global elimination of HCV infection.

Introduction

Globally, it is estimated that 71.1 million people have chronic hepatitis C virus (HCV) infection (The Polaris Observatory, 2017), including an estimated 7.5 million people who have recently injected drugs (PWID) (Nelson et al., 2011). There is an additional large, but unquantified, burden among those PWID who have ceased injecting (Hajarizadeh, Grebely, & Dore, 2013; Nelson et al., 2011). The incidence of HCV infection among current PWID also remains high in many settings (Morris et al., 2017a; Page, Morris, Hahn, Maher, & Prins, 2013). Morbidity and mortality due to liver disease among PWID with HCV infection continues to increase (Hajarizadeh et al., 2013), despite the advent of well-tolerated, simple interferon-free direct-acting antiviral (DAA) HCV regimens with cure rates >95% (Dore & Feld, 2015). As a result of this important clinical breakthrough, there is potential to reverse the rising burden of advanced liver disease with increased treatment and strive for HCV elimination among PWID and those who have ceased injecting.

Unfortunately, there are many gaps in knowledge that represent barriers to effective prevention and management of HCV among PWID. The Kirby Institute, UNSW Sydney and the International Network of Hepatitis in Substance Users (INHSU) established an expert round table panel to assess current research gaps and establish future research priorities for the epidemiology, prevention, and management of HCV among PWID. This round table consisted of a one-day workshop held on 6 September, 2016, in Oslo, Norway, prior to the International Symposium on Hepatitis in Substance Users (INHSU 2016). International experts in drug and alcohol, infectious diseases, and hepatology were brought together to discuss the available scientific evidence, gaps in research, and develop research priorities. Topics for discussion included the epidemiology of injecting drug use, HCV, and HIV among PWID, HCV prevention, HCV testing, linkage to HCV care and treatment, DAA treatment for HCV infection, and reinfection following successful treatment.

Section snippets

Epidemiology of injecting drug use, HCV, and HIV among PWID

People with a history of injecting drug use include those who report injecting an illicit drug at least once in their life. This population includes people who have permanently ceased injecting; “current” or “recent” injectors (with definitions for “recent” varying in the literature from one month to one year); as well as people who may be considered “occasional” injectors (including people in treatment for drug use disorders, some may be receiving opioid substitution therapy (OST), who have

Prevention of primary HCV infection

HCV incidence remains high in many settings (Hagan, Pouget, Des Jarlais, & Lelutiu-Weinberger, 2008; Morris et al., 2017a, Page et al., 2013, Wiessing et al., 2014), particularly in the first several years of injecting (Hagan et al., 2008; Roy, Boudreau, & Boivin, 2009), and ongoing HCV transmission is a major issue among PWID, with variations globally.

There is no HCV vaccine, either currently or readily foreseeable. A mathematical model recently suggested that a partially effective vaccine,

HCV testing

Simple, tolerable, and effective DAA HCV therapies have eliminated interferon as a major barrier to HCV scale-up in PWID and dramatically simplified diagnostic and monitoring needs (Cohn, Roberts, Amorosa, Lemoine, & Hill, 2015). However, in order for these therapies to have an effect at a population level (Grebely & Dore, 2014), targeted interventions to enhance HCV testing, linkage to care, and treatment (“the HCV care cascade”) are needed.

Globally, HCV testing and diagnosis remains

Linkage to HCV care and treatment

Linkage to HCV care and treatment also remains inadequate internationally (Bruggmann et al., 2014, Liakina et al., 2015, Saraswat et al., 2015). Simplified HCV testing, including dried blood spot testing (McAllister et al., 2014) and point-of-care HCV testing (Bottero et al., 2015, Morano et al., 2014) has been shown to facilitate linkage to HCV care. Other strategies that have been demonstrated to facilitate linkage to HCV care and treatment include, non-invasive liver disease screening using

DAA treatment for HCV infection

The availability of tolerable, highly effective all-oral DAA regimens has overcome the barrier posed by poor tolerability of interferon-based therapy, providing an important tool to achieve scale-up of HCV therapy in PWID.

Among people receiving OST with no recent illicit drug use, post-hoc analyses of phase II and III trials of DAA therapy have demonstrated that treatment completion, adherence, and sustained virological response (SVR) are similar to those not receiving OST (Dore et al., 2016,

Reinfection following successful treatment

Ongoing risk behaviours following successful HCV therapy and lack of adequate coverage of harm reduction interventions (e.g. NSP and OST) may lead to reinfection and compromised treatment outcomes (Cunningham, Applegate, Lloyd, Dore, & Grebely, 2015; Midgard et al., 2016). The incidence of HCV reinfection following successful interferon-based treatment among PWID ranges from 0.0 to 5.3/100 person-years (Aspinall et al., 2013, Cunningham et al., 2015, Midgard et al., 2016, Pineda et al., 2015;

Approach to these research priorities

A further consideration is the methods chosen to address these identified research priorities. This expert panel identified that a multi-disciplinary and multi-method approach is appropriate for these research priorities. In particular, the expertise and insight that can be drawn from social science and from direct involvement of the affected communities was highlighted as best and appropriate practice to optimise investment in HCV research.

Each of the research priorities posed across topics

Conclusion

The high burden of HCV infection among populations of PWID poses challenges for the implementation of evidence-based, best practice guidelines to shape the priorities that are identified for research. A key underpinning to research in each area of epidemiology, prevention, testing, linkage to care, treatment outcomes and reinfection is the prohibition that surrounds injecting drug use around the globe. Hence, a research question that is relevant to each area is the impact of policies and

Financial support

The Kirby Institute is funded by the Australian Government Department of Health. The National Drug and Alcohol Research Centre at UNSW Australia is supported by funding from the Australian Government under the Substance Misuse Prevention and Service Improvements Grant Fund. The views expressed in this publication do not necessarily represent the position of the Australian Government. JG is supported by a National Health and Medical Research Council Career Development Fellowship. LD is supported

Disclosures

JG is a consultant/advisor and has received research grants from Abbvie, Bristol Myers Squibb, Cepheid, Gilead Sciences and Merck. PB has served as advisor and speaker for, and has received project and research grants from AbbVie, BMS, Gilead, Merck, and Mundipharma. JVL is a consultant/advisor for Gilead Sciences and MSD and has received research grants from AbbVie and Gilead Sciences. MaHe received investigator initiated research grant support from Abbvie, Bristol Myers Squibb, and Gilead

References (137)

  • J. Grebely et al.

    Recommendations for the management of hepatitis C virus infection among people who inject drugs

    International Journal on Drug Policy

    (2015)
  • M. Harris

    Managing expense and expectation in a treatment revolution: Problematizing prioritisation through an exploration of hepatitis C treatment ‘benefit’

    International Journal of Drug Policy

    (2017)
  • M. Harris et al.

    The promise of treatment as prevention for hepatitis C: Meeting the needs of people who inject drugs?

    International Journal of Drug Policy

    (2015)
  • M. Harris et al.

    Taming systems to create enabling environments for HCV treatment: Negotiating trust in the drug and alcohol setting

    Social Science and Medicine

    (2013)
  • A. Jewett et al.

    Field-based performance of three pre-market rapid hepatitis C virus antibody assays in STAHR (Study to Assess Hepatitis C Risk) among young adults who inject drugs in San Diego, CA

    Journal of Clinical Virology

    (2012)
  • J. Lalezari et al.

    Ombitasvir/paritaprevir/r and dasabuvir plus ribavirin in HCV genotype 1-infected patients on methadone or buprenorphine

    Journal of Hepatology

    (2015)
  • F.M.J. Lamoury et al.

    Hepatitis C virus core antigen: A simplified treatment monitoring tool, including for post-treatment relapse

    Journal of Clinical Virology

    (2017)
  • S. Larney et al.

    Defining populations and injecting parameters among people who inject drugs: Implications for the assessment of hepatitis C treatment programs

    International Journal on Drug Policy

    (2015)
  • A.H. Litwin et al.

    Primary care-based interventions are associated with increases in hepatitis C virus testing for patients at risk

    Digestive and Liver Disease

    (2012)
  • G.J. MacArthur et al.

    Interventions to prevent HIV and hepatitis C in people who inject drugs: A review of reviews to assess evidence of effectiveness

    International Journal on Drug Policy

    (2014)
  • A.D. Marshall et al.

    Liver disease knowledge and acceptability of non-invasive liver fibrosis assessment among people who inject drugs in the drug and alcohol setting: The LiveRLife study

    International Journal on Drug Policy

    (2015)
  • N.K. Martin et al.

    Prioritization of HCV treatment in the direct-acting antiviral era: An economic evaluation

    Journal of Hepatology

    (2016)
  • N.K. Martin et al.

    Can antiviral therapy for hepatitis C reduce the prevalence of HCV among injecting drug user populations? A modeling analysis of its prevention utility

    Journal of Hepatology

    (2011)
  • K. Mason et al.

    Understanding Real-World Adherence in the Directly Acting Antiviral Era: a prospective evaluation of adherence amongst people with a history of drug use at a community-based program in Toronto, Canada

    International Journal of Drug Policy

    (2017)
  • P. Mateu-Gelabert et al.

    How can hepatitis C be prevented in the long-term?

    International Journal of Drug Policy

    (2007)
  • B.M. Mathers et al.

    HIV prevention, treatment, and care services for people who inject drugs: A systematic review of global, regional and national coverage

    The Lancet

    (2010)
  • B.M. Mathers et al.

    Global epidemiology of injecting drug use and HIV among people who inject drugs: A systematic review

    The Lancet

    (2008)
  • G. McAllister et al.

    Uptake of hepatitis C specialist services and treatment following diagnosis by dried blood spot in Scotland

    Journal of Clinical Virology

    (2014)
  • J.P. Meyer et al.

    Evidence-based interventions to enhance assessment, treatment, and adherence in the chronic hepatitis C care continuum

    International Journal on Drug Policy

    (2015)
  • H. Midgard et al.

    Hepatitis C reinfection after sustained virological response

    Journal of Hepatology

    (2016)
  • L. Morris et al.

    Initial outcomes of integrated community-based hepatitis C treatment for people who inject drugs: findings from the Queensland Injectors#xp# Health Network

    International Journal of Drug Policy

    (2017)
  • P.K. Nelson et al.

    Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: Results of systematic reviews

    The Lancet

    (2011)
  • D.J. Nutt et al.

    Drug harms in the UK: A multicriteria decision analysis

    The Lancet

    (2010)
  • B. Paterson et al.

    The depiction of stigmatization in research about hepatitis C

    International Journal of Drug Policy

    (2007)
  • B. Paterson et al.

    Structural factors that promote stigmatization of drug users with hepatitis C in hospital emergency departments

    International Journal of Drug Policy

    (2013)
  • J.A. Pineda et al.

    Hepatitis C virus reinfection after sustained virological response in HIV-infected patients with chronic hepatitis C

    Journal of Infection

    (2015)
  • AASLD/IDSA

    Recommendations for testing, managing, and treating hepatitis C

    (2015)
  • M.T. Abou-Saleh et al.

    Hepatitis C testing in drug users using the dried blood spot test and the uptake of an innovative self-administered DBS test

    Addictive Disorders & Their Treatment

    (2013)
  • S. Arora et al.

    Outcomes of treatment for hepatitis C virus infection by primary care providers

    The New England Journal of Medicine

    (2011)
  • 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)
  • C.G. Beckwith et al.

    A pilot study of rapid hepatitis C virus testing in the Rhode Island Department of Corrections

    Journal of Public Health

    (2016)
  • L. Boglione et al.

    Treatment with direct-acting antiviral agents of hepatitis C virus infection in injecting drug users: A prospective study

    Journal of Viral Hepatitis

    (2017)
  • J. Bottero et al.

    Simultaneous human immunodeficiency virus-hepatitis B-hepatitis C point-of-care tests improve outcomes in linkage-to-care: Results of a randomized control trial in persons without healthcare coverage

    Open Forum Infectious Diseases

    (2015)
  • L. Brener et al.

    Discrimination by health care workers versus discrimination by others: Countervailing forces on HCV treatment intentions

    Psychology, Health & Medicine

    (2015)
  • P. Bruggmann et al.

    Historical epidemiology of hepatitis C virus (HCV) in selected countries

    Journal of Viral Hepatitis

    (2014)
  • P. Bruggmann et al.

    Models of care for the management of hepatitis C virus among people who inject drugs: One size does not fit all

    Clinical Infectious Diseases

    (2013)
  • Canadian HIV/AIDS Legal Network

    Nothing about us without us, greater, meaningful involvement of people who use illegal drugs: A public health, ethical, and human rights imperative

    (2005)
  • J. Cohn et al.

    Simplified diagnostic monitoring for hepatitis C, in the new era of direct-acting antiviral treatment

    Current Opinion in HIV and AIDS

    (2015)
  • B. Conway et al.

    Efficacy of all-oral HCV therapy in people who inject drugs

    Hepatology

    (2016)
  • N. Craine et al.

    Improving blood-borne viral diagnosis; clinical audit of the uptake of dried blood spot testing offered by a substance misuse service

    Journal of Viral Hepatitis

    (2009)
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