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Randomized Controlled Trial
. 2021 Jun 1;18(6):e1003653.
doi: 10.1371/journal.pmed.1003653. eCollection 2021 Jun.

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

Lars T Fadnes  1   2 , Christer Frode Aas  1   2 , Jørn Henrik Vold  1   2 , Rafael Alexander Leiva  3 , Christian Ohldieck  1 , Fatemeh Chalabianloo  1   2 , Svetlana Skurtveit  4   5 , Ole Jørgen Lygren  1   6 , Olav Dalgård  7   8 , Peter Vickerman  9 , Håvard Midgard  7   10 , Else-Marie Løberg  1   11   12 , Kjell Arne Johansson  1   2 ; INTRO-HCV Study Group
Affiliations
Randomized Controlled Trial

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

Lars T Fadnes et al. PLoS Med. .

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.

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Conflict of interest statement

The authors LTF, CFA, JHV, SS, CO, FC, EML, KAJ, have declared that no competing interests exist. We have read the journal’s policy and these authors of this manuscript have the following competing interests: AL has received lecture and advisory fees from Gilead, GSK and MSD. OJL has received project grants from AbbVie, Gilead and MSD. OD has received research grants from and been in advisory board for MSD, Abbvie and Gilead. PV has received an unrestricted research grant off Gilead. HM has received lecture and advisory fees from Gilead, Abbvie and MSD.

Figures

Fig 1
Fig 1. Trial profile for the study.
*Estimated numbers. HCV, hepatitis C infection; OAT, opioid agonist therapy; PWID, people who inject drugs.
Fig 2
Fig 2. Time to hepatitis C treatment initiation presented with Kaplan–Meier plot.
Red line/area indicates proportion of participants in integrated arm initiation treatment with confidence intervals. Blue dashed line/area indicates proportion of participants in standard treatment arm initiation treatment.
Fig 3
Fig 3. Subgroup analyses for binomial logit regression of SVR of hepatitis C for those who initiated treatment comparing the integrated arm with the standard arm (post hoc ITT analyses).
Subgroup effects are presented for gender, the type of treatment center, age group, living condition, injecting drug use behavior the last 6 months, fibrosis and cirrhosis, and overall effects (without and with cluster adjustment)**. *Non-OAT: patients who did not receive OAT. **Interaction tests: sex: p = 0.069, site: p = 0.737, OAT/non-OAT: p = 0.095, age: p = 0.023, living condition: p = 0.367, injecting drugs: p = 0.309, fibrosis/cirrhosis: p = 0.605. ITT, intention-to-treat; OAT, opioid agonist therapy; OR, odds ratio; SVR, sustained virologic response.
Fig 4
Fig 4. Subgroup analyses for binomial logit regression of SVR of hepatitis C for all who were randomized comparing the integrated arm with the standard arm (post hoc ITT analyses).
Subgroup effects are presented for gender, the type of treatment center, age group, living condition, injecting drug use behavior the last 6 months, fibrosis and cirrhosis, and overall effects (without and with cluster adjustment)**. *Non-OAT: patients who did not receive OAT. **Interaction tests: sex: p = 0.231, site: p = 0.358, OAT/non-OAT: p = 0.237, age: p = 0.041, living condition: p = 0.928, injecting drugs: p = 0.972, fibrosis/cirrhosis: p = 0.382. ITT, intention-to-treat; OAT, opioid agonist therapy; OR, odds ratio; SVR, sustained virologic response.
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