Integrated treatment of hepatitis C virus infection among people who inject drugs: A multicenter randomized controlled trial (INTRO-HCV)

Lars T Fadnes; Christer Frode Aas; Jørn Henrik Vold; Rafael Alexander Leiva; Christian Ohldieck; Fatemeh Chalabianloo; Svetlana Skurtveit; Ole Jørgen Lygren; Olav Dalgård; Peter Vickerman; Håvard Midgard; Else-Marie Løberg; Kjell Arne Johansson; INTRO-HCV Study Group

doi:10.1371/journal.pmed.1003653

Integrated treatment of hepatitis C virus infection among people who inject drugs: A multicenter randomized controlled trial (INTRO-HCV)

PLoS Med. 2021 Jun 1;18(6):e1003653. doi: 10.1371/journal.pmed.1003653. eCollection 2021 Jun.

Authors

Lars T Fadnes^{1

2}, Christer Frode Aas^{1

2}, Jørn Henrik Vold^{1

2}, Rafael Alexander Leiva³, Christian Ohldieck¹, Fatemeh Chalabianloo^{1

2}, Svetlana Skurtveit^{4

5}, Ole Jørgen Lygren^{1

6}, Olav Dalgård^{7

8}, Peter Vickerman⁹, Håvard Midgard^{7

10}, Else-Marie Løberg^{1

11

12}, Kjell Arne Johansson^{1

2}; INTRO-HCV Study Group

Affiliations

¹ Bergen Addiction Research, Department of Addiction Medicine, Haukeland University Hospital, Norway.
² Department of Global Public Health and Primary Care, University of Bergen, Norway.
³ Department of Medicine, Haukeland University Hospital, Norway.
⁴ Norwegian Centre for Addiction Research, University of Oslo, Norway.
⁵ Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway.
⁶ ProLAR Nett, Norway.
⁷ Department of Infectious Diseases, Akershus University Hospital, Lørenskog, Norway.
⁸ Institute for Clinical Medicine, University of Oslo, Norway.
⁹ Population Health Sciences, Bristol Medical School, University of Bristol, United Kingdom.
¹⁰ Department of Gastroenterology, Oslo University Hospital, Norway.
¹¹ Department of Clinical Psychology, University of Bergen, Norway.
¹² Division of Psychiatry, Haukeland University Hospital, Norway.

Abstract

Background: The standard pathways of testing and treatment for hepatitis C virus (HCV) infection in tertiary healthcare are not easily accessed by people who inject drugs (PWID). The aim of this study was to evaluate the efficacy of integrated treatment of chronic HCV infection among PWID.

Methods and findings: INTRO-HCV is a multicenter, randomized controlled clinical trial. Participants recruited from opioid agonist therapy (OAT) and community care clinics in Norway over 2017 to 2019 were randomly 1:1 assigned to the 2 treatment approaches. Integrated treatment was delivered by multidisciplinary teams at opioid agonist treatment clinics or community care centers (CCCs) for people with substance use disorders. This included on-site testing for HCV, liver fibrosis assessment, counseling, treatment, and posttreatment follow-up. Standard treatment was delivered in hospital outpatient clinics. Oral direct-acting antiviral (DAA) medications were administered in both arms. The study was not completely blinded. The primary outcomes were time-to-treatment initiation and sustained virologic response (SVR), defined as undetectable HCV RNA 12 weeks after treatment completion, analyzed with intention to treat, and presented as hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals. Among 298 included participants, 150 were randomized to standard treatment, of which 116/150 (77%) initiated treatment, with 108/150 (72%) initiating within 1 year of referral. Among those 148 randomized to integrated care, 145/148 (98%) initiated treatment, with 141/148 (95%) initiating within 1 year of referral. The HR for the time to initiating treatment in the integrated arm was 2.2 (1.7 to 2.9) compared to standard treatment. SVR was confirmed in 123 (85% of initiated/83% of all) for integrated treatment compared to 96 (83% of initiated/64% of all) for the standard treatment (OR among treated: 1.5 [0.8 to 2.9], among all: 2.8 [1.6 to 4.8]). No severe adverse events were linked to the treatment.

Conclusions: Integrated treatment for HCV in PWID was superior to standard treatment in terms of time-to-treatment initiation, and subsequently, more people achieved SVR. Among those who initiated treatment, the SVR rates were comparable. Scaling up of integrated treatment models could be an important tool for elimination of HCV.

Trial registration: ClinicalTrials.gov.no NCT03155906.

Publication types

Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antiviral Agents / therapeutic use*
Delivery of Health Care, Integrated*
Drug Users*
Female
Hepatitis C, Chronic / complications
Hepatitis C, Chronic / diagnosis
Hepatitis C, Chronic / drug therapy*
Humans
Male
Middle Aged
Norway
Opiate Substitution Treatment*
Substance Abuse, Intravenous / complications
Substance Abuse, Intravenous / diagnosis
Substance Abuse, Intravenous / rehabilitation*
Sustained Virologic Response
Time Factors
Treatment Outcome
Viral Load

Substances

Antiviral Agents

Associated data

ClinicalTrials.gov/NCT03155906

Grants and funding

The INTRO-HCV study was funded by The Norwegian Research Council (BEHANDLING, funding no 269855, grant received by LTF et al.) and the Western Norway Regional Health Authority (Helse Vest «Åpen prosjektstøtte», grant received by LTF et al.) with the Department of Addiction Medicine, Haukeland University Hospital as the responsible institution. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.