Integrated treatment of hepatitis C virus infection among patients with injecting drug abuse: a randomised controlled trial (INTRO HCV)

Patients with drug addiction have a high disease burden, generally have more difficulties in obtaining adequate health care compared with the general population, on top of knowledge gaps on health status and how to deliver proper treatment and follow-up. Reports from clinics delivering opioid agonist therapy (OAT) in Norway indicate that more than half of the patients receiving OAT had a chronic hepatitis C virus infection (HCV). Chronic HCV substantially increases the risk of severe complications such as liver failure and death within two to three decades. However, only around a third of OAT patients with chronic HCV had received HCV treatment when we started our study in 2017. Thus, there is a need for new approaches to reach more of patients with drug addiction in need of treatment while ensuring high-quality care. To succeed in this, an integrated model of health care was tested in a large randomized controlled clinical trial where we assessed integrated HCV treatment within the OAT clinics compared to standard treatment. The integrated treatment model focused on inter-disciplinarity, accessibility, more patient-centred and less invasive follow-up requiring less blood samples taken (including one single blood sample prior to treatment with chained testing for antibodies, hepatitis virus and quantification and genotyping of hepatitis C). It involved close and frequent follow-up availability linked with other treatments, without requiring substantial additional time or visits from the patients. In the trial, half of 298 persons were randomized to receive integrated treatment and the other half received treatment; all with direct acting antiviral medications. The results confirmed our hypotheses. Among those receiving integrated treatment, 98% initiated treatment for HCV while 77% initiated among those receiving standard treatment. Treatment was initiated double as fast among those receiving integrated treatment. Further, 93% of those randomized to integrated treatment had sustained virologic response compared to 73% among those receiving standard treatment. Time to sustained virologic response was halved among those receiving integrated treatment. There were no serious adverse events considered to be related with the treatment. The treatment was effective both for women and men, among the youngest and oldest participants, among those receiving opioid agonist therapy and those receiving municipal care services, those with stable and unstable living conditions, and among those who still injected drugs. The treatment was also found to be highly cost effective in both Norway and in several other countries, and probably also cost saving in Norway and in several other settings. Preliminary assessment of prevalence of hepatitis C among people who inject/have injected drugs in the largest cities in Western Norway (Bergen and Stavanger), showed a reduction in the prevalence of hepatitis C from 54% in 2017 to 7% in 2020. This is a reduction of 87% in three years and these areas are probably in line with the ambitious targets to reduce the prevalence of hepatitis C by 90% by 2023, aiming for elimination of hepatitis C. The importance of integrated treatment models has now been emphasized both in Norwegian and international guidelines on treatment of hepatitis C where our study is one of the drivers behind this change. If this treatment model is scaled up, this could contribute to elimination of HCV, both locally, nationally and internationally.

The primary objectives of the project 1. We estimate incidence and prevalence of HCV infection among people who inject drugs in Bergen- and the Stavanger being followed up at OAT outpatient clinics or people who inject drugs followed up at primary health care clinics. The overall prevalence when we started in 2017 were 54% and in 2020 the prevalence was 7%. 2. We compared the effect of integrated HCV treatment between the OAT outpatient clinics in Bergen and Stavanger (intervention arm) with standard treatment provided after referral to infectious disease clinics among patients who receive OAT having HCV. Among those receiving integrated treatment, 98% initiated treatment for HCV while 77% initiated among those receiving standard treatment. Treatment was initiated double as fast among those receiving integrated treatment. Secondary objectives: 1. We assessed the proportion with sustained virologic response (successfully treated for hepatitis C). Of those randomized to integrated treatment, 93% had sustained virologic response compared to 73% among those receiving standard treatment. Time to sustained virologic response was halved among those receiving integrated treatment. 2. We aimed to compare treatment adherence between the intervention and control arms, and the risk of reinfection among those with sustained virologic response. These analyses are not yet completed. 3. We aimed to assess changes in quality of life, fatigue, and psychological well-being, drug use and infection related risk behaviour before and after HCV treatment. Relating to change in fatigue and quality of life, our analyses has shown that those receiving integrated treatment had slightly ore reduction in symptoms of fatigue, and reported more hope relating to the future. Qualitative data on substance use, indicated that many reported that treatment of hepatitis C had contributed to reducing their substance use. Relating to psychological distress, adherence of treatment, and re-infection, these will be analysed further and are likely to be submitted for publication within the next months. Societal impacts Our project contributed to a reduction of 87% in three years in the prevalence of hepatitis C in the largest cities in Western Norway. These areas are now on track to the ambitious targets to reduce the prevalence of hepatitis C by 90% by 2023, aiming for elimination of hepatitis C. The importance of integrated treatment models has now been emphasized both in Norwegian and international guidelines on treatment of hepatitis C where our study is one of the drivers behind this change. If this treatment model is scaled up, this could contribute to elimination of HCV, both locally, nationally, and internationally.

Patients with drug addiction have a high disease burden, generally have more difficulties in obtaining adequate health care compared with the general population, on top of knowledge gaps on health status and how to deliver ¬proper treatment and follow-up. Reports from clinics delivering opioid substitution therapy (OST) in Norway indicate that more than half of the patients receiving OST have a chronic hepatitis C virus infection (HCV). Chronic HCV substantially increases the risk of severe complications such as liver failure and death within two to three decades. However, only around 14% of OST patients with chronic HCV have received HCV treatment yet. Thus, there is a need for new approaches to reach more of patients with drug addiction in need of treatment while ensuring high-quality care. To succeed in this, a model of health care focusing on interdisciplinarity, accessibility, close and frequent follow-ups, seems to be necessary. Such a model has been adopted by Department of Addiction Medicine in Bergen and OST in Stavanger, which is unique in a national and international perspective. This makes it an excellent platform to test out integration of HCV treatment aiming to improve health and life span of a vulnerable group, and at the same time gathering knowledge which traditionally has been difficult to obtain. We will conduct a large randomised controlled clinical trial where we will assess integrated HCV treatment within the OST clinics compared to standard treatment. We will develop a regional OST data registry and biobank as part of the data collection, which will contribute to future research and evidence on drug addiction. The large regional collaboration in this research project between several institutions in Bergen, Stavanger and Sandnes including specialist and municipal primary health care, strong involvement of user organisations, as well as researchers from Bergen, Stavanger and Oslo, could establish a model for potential future national scale-up.