People living with a substance use disorder (SUD) are a key population within the hepatitis C virus (HCV) epidemic. Specifically, the estimated global HCV prevalence among people who inject drugs (PWID) is 67%, or approximately 10 million individuals, with incidence rates ranging from 5% to 45% per year [1]. PWID constitute approximately 14% of the 71 million people infected with HCV globally [2]. Due to similar transmission routes, there is overrepresentation of PWID among individuals who are co-infected with HCV and HIV, with over half of the 2.3 million globally co-infected individuals being among PWID [3,4]. PWID are not only at greater risk of HCV infection (and re-infection), but also at increased risk of disease progression, mortality, and onward HCV transmission due to various socio-structural and environmental exposures, including poor access to health care services, socioeconomic marginalization, and the persistence of law enforcement-based responses to illicit drug use [1,5-7]. While HCV is mainly transmitted via injection drug use, non-injection drug use has also been associated with HCV infection. For example, there is some evidence of HCV transmission via crack pipe sharing [8], and among men who have sex with men who use non-intravenous drugs [9,10]. HCV prevalence is higher in non-injecting drug users than in nondrug users. Moreover, many PWID are polysubstance users with non-injection drugs [11].

Despite the advent of safe and highly efficacious direct-acting antiviral–based therapy, resulting in the possibility of controlling the HCV epidemic, concerns regarding treatment access, adherence, and potential reinfection, particularly among marginalized populations such as PWID, remain [5,6]. Indeed, access and uptake of HCV treatment has been consistently low among PWID, with studies indicating that only 1%-6% of this population has ever been treated with interferon-based therapies [12-14]. The reluctance of physicians to treat HCV infection in PWID is likely due to the stigma and discrimination that continue to persist among this population [15]. Low treatment rates among this population may also reflect PWIDs’ fear of treatment, competing priorities (eg, active illicit drug use), as well as general barriers to accessing healthcare [16,17]. Moreover, in some jurisdictions, the high cost of direct-acting antivirals (DAA) treatment is only covered provided that the patient meets specific criteria (eg, a fibrosis score of 2 or more) [18]. As such, the high cost of DAA may also constitute a barrier to treatment for PWID who do not meet these criteria, or who live in settings where DAA treatment is not covered. Nevertheless, recent studies have shown that, when appropriately supported, PWID are able to achieve similar rates of sustained virologic response compared to the general population [19,20].

Prior reviews have explored integrated models of care in the context of HIV, and these have been shown to have a significant beneficial impact on the treatment and health outcomes of PWID, particularly when coupled with SUD services [21]. Similarly, emerging studies have suggested the importance of opioid agonist therapy (OAT) and mental health services on reducing the risk of HCV reinfection among this population [19,22-24]. However, there has been no explicit systematic review conducted on the impact of HCV and SUD integrated programs and services on HCV, and addiction treatment and health outcomes among individuals living with these comorbid diseases. This review will address an important gap in the literature by comprehensively assessing the available literature to provide insight into effective and efficient models of care for people living with HCV and SUD.

The current protocol has been registered in the PROSPERO CRD42017078445 and conforms to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) checklist (Multimedia Appendix 1). We will also adhere to the PRISMA guidelines for the development of this systematic review report [25].

We have received funding from the Canadian Institute of Health Research, allowing the commencement of the project. To date, we have completed the search strategy. We obtained 1711 records after duplicates were removed. After screening the titles and abstracts, 153 full-texts were reviewed. Of those, 57 were excluded and 96 will be included in the qualitative synthesis. After hand-searching conferences abstracts, 36 were selected for inclusion. We are currently in the process of grading the selected full-texts, and qualitative synthesis of the findings is currently under way. We expect the final results to be submitted for publication in the fall of 2018.

To our knowledge, this systematic review will be the first to synthesize the available evidence on the integration of HCV and substance use services on treatment, health, and cost-related outcomes. Identification and implementation or adaption of different integrated models of care to improve the health and well-being of people living with HCV and an SUD may have a significant impact on reducing the negative health and social consequences associated with these comorbid diseases, as well as healthcare utilization costs, and resource burden on the healthcare system. The results of this systematic review may guide future research in this area and contribute to the development of evidence-based policies and programs for the treatment and care of people living with HCV and an SUD.

We plan to implement a comprehensive end-of-project knowledge translation strategy to ensure that the findings of this research are accessible to key stakeholders. Specifically, we will present the results of this review at relevant HCV and substance use meetings nationally and internationally, as well as publish in an open access peer-reviewed journal in an effort to increase access for appropriate scientific, clinical, and public audiences. Lastly, we plan to collaborate with relevant clinical programs and community organizations to ensure the timely and effective application of the research findings. Specifically, we will organize plain language presentations of our research findings with time for discussion and feedback, we will attend meetings and planning discussions with health authorities and health administrators, and we will reach out to policy-makers via briefing notes or other venues.

There are several limitations that should be noted. The expected heterogeneity of the literature on integrated models of care may affect our ability to draw clear conclusions from the literature. Additionally, we recognize that the selection and qualitative synthesis of the eligible studies is a subjective process; however, we will seek to minimize this limitation by duplicating our search and utilizing two reviewers to conduct the screening and quality assessment processes independently. As with all reviews, it is possible that some eligible studies may be missed in our search strategy. To minimize this limitation, we have kept our search strategy relatively broad and have sought input from an experienced librarian. Lastly, there may be a publication bias observed as a general limitation of systematic reviews. We will try to minimize this issue by searching databases for unpublished studies (eg, ClinicalTrials.gov).

In sum, this systematic review will synthesize the available evidence on the integration of HCV and substance use services and its impact on various outcomes, including health- and cost-related outcomes. It is expected that the findings from this review will provide evidence towards the effective delivery of healthcare programs and services for people living with HCV and an SUD.