Integrated Treatment of Hepatitis C Virus Infection Among Patients With Injecting Drug Abuse:a Randomised Controlled Trial (INTRO-HCV)

Rationale Globally, about 71 million people are chronically infected with chronic hepatitis C virus infection (HCV) and approximately 700,000 are dying annually of related complications. It has been estimated to be 10-20,000 people in Norway have chronic HCV. People who inject drugs represent around 75% of these, most being infected with HCV through sharing of syringes and other user equipment. HCV and hepatitis B are both among the leading causes to liver disease and transplantation worldwide. Prevention and control has to date unfortunately shown to be difficult.

Among people with opioid addiction and HCV, a third develops severe complications within three decades. Within the same group and after 50 years of age, liver disease is as common as risk of death as overdose. Reports from medically assisted rehabilitation (MAR) clinics delivering opioid substitution therapy (OST) in Norway indicate that more than half of the patients receiving OST have a HCV. Chronic HCV substantially increases the risk of severe complications such as liver failure and death within two to three decades. The mean age of OST patients in Norway is 42 years and is currently increasing, and a large group have had HCV for more than twenty years. Reaching these patients with treatment is of critical importance to avoid deaths and reduced quality of life, as well as preventing large costs related to future treatment of end stage liver disease. Treatment for HCV has been available for several decades, and weekly injections with interferon in combination with daily ribavirin tablets for 16 to 48 weeks has until recently been the standard treatment. These medications have been shown to give frequent and to some degree serious side effects, with around 40% not achieving sustained virological response (SVR). These aspects combined with a fear among many clinicians of reinfection among those being treated and an expectation of poor treatment adherence in this group, has probably been the reasons for few patients having been treated yet. However, studies assessing treatment adherence indicate good adherence among patients receiving OST. Even if around 6% of those who are successfully treated among people who inject drugs are reinfected annually, treatment is not only important for those who are treated, but will also contribute to reduce the HCV infectious burden and the risk of spread within the population.

During the last years, development of new highly effective tablet-based direct acting antiretroviral medications, usually being curative within 8 to 16 weeks, has radically changed the HCV treatment. These treatments have less side effects than those used earlier and give opportunities to cure most of the HCV infected. Even if they are expensive, British assessments indicate that they are cost effective as universal coverage with antiretroviral treatment could prevent large expenses related to future complications. Thus, the Norwegian Medicines Agency approved many of these new antiretroviral treatments in 2014. Nevertheless, a recent Norwegian study indicated that only 14% of OST patients with chronic HCV had received HCV treatment. Currently, the high burden of HCV among people who inject drugs is among the largest challenges within the MAR field, within a group that is also underrepresented in clinical research.

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 in terms of health status and how to deliver proper treatment and follow-up. This is particularly the case among people who inject drugs.

There is a need for new approaches to reach more of those in need of treatment while ensuring high-quality care. To reach patients with drug addiction, it seems to be necessary to use a model of health care focusing on interdisciplinarity, accessibility, close and frequent follow-ups.