Current Models to Address Obstacles to HCV Elimination

Abstract

To help inspire global action, the World Health Organization (WHO) has set an ambitious goal of eliminating viral hepatitis, including hepatitis C virus (HCV) infection, as a public health concern by 2030. Globally, an estimated 58 million people have chronic HCV infection, including over 4.5 million people who have recently injected drugs (PWID). Of the 1.5 million new infections occurring per year, over 43% are in this risk group. Systematic approaches are needed with this population to achieve the WHO elimination goals. A number of programs have been successful, most notably in Australia, Scotland, Iceland and North America. We still require additional programs that are easily accessible, multidisciplinary, durable and driven by patient-defined parameters of engagement. We have evaluated housing-based programs as community pop-up clinics to identify HCV-infected vulnerable inner-city residents and offer HCV treatment within such a context. This has been successful, with almost 300 individuals receiving treatment since January 2021, with an effective cure rate exceeding 98%, 99% retention in care, HCV reinfection rates below 1/100 person-years and reduced rates of opioid-related overdose deaths. The implementation of programs, such as ours, must be considered to achieve elimination of HCV infection among PWID on a worldwide basis.

1. Introduction

Hepatitis C virus (HCV) infections represent one of the leading causes of liver disease and associated morbidity and mortality, affecting over 58 million people worldwide, including over 4.5 million people who inject drugs (PWIDs) [1]. Indeed, drug use (especially injection drug use) currently represents the main risk factor for HCV transmission in the western world. Between 2005 and 2015, the new cases of HCV have increased threefold in this population and roughly 50% of PWIDs have been infected with HCV [2]. In some jurisdictions, the prevalence of HCV infection in drug users approaches 80%, often representing the largest group of infected individuals.

In 2019 it was estimated that there were 171,900 PWIDs living in Canada with an HCV seroprevalence of about 62% [3]. PWIDs make up between 60% and 85% of all incident infections acquired from sharing needles and other drug using equipment [4]. Other risk factors that increase the likelihood of unsafe practices and increased exposure to HCV (but also to other blood borne diseases, such as HIV and HBV) include experiences of homelessness, arrests, incarceration, sex work and mental and emotional instability [5, 6, 7, 8, 9]. All these aspects are key factors that need to be addressed when considering optimal HCV treatment strategies for this particular population, in order to maximize engagement in care, including the provision of HCV therapy.

In 2016, the World Health Organization (WHO) set the goal and outlined the strategies for elimination of HCV infection (and also hepatitis B infection) as a public health concern by 2030. For HCV infection, this would require a reduction in the incidence of new infections and mortality by 90 and 65%, respectively, compared to the values reported at baseline (2015). To achieve these targets, many countries have attempted to profile specific interventions to promote HCV elimination. However, many challenges and barriers to HCV eradication remain [10, 11]. Firstly, diagnosis of HCV infection and provision of treatment is difficult because most individuals are asymptomatic, unaware of their disease status and poorly motivated to seek care. Indeed, many wait until disease progression has occurred (advanced cirrhosis, hepatocellular carcinoma and other severe HCV-related complications), limiting the expected benefit of antiviral treatment and increasing disease transmission over years as they remain untreated. Therefore, screening of specific subpopulations with high incidence rates, such as PWIDS, is recommended [11]. Modeling exercises suggest that, simply by addressing HCV in this population, we will reduce new HCV infections by over 40%. The results of such interventions have been mixed, at best. Moreover, the spread of SARS-CoV-2 since the beginning of 2020 and the restrictive measures applied to contain the infection had a direct impact on the health care system in general, especially non-essential services. Among the many consequences of the pandemic and the public health response to it, there has been a disruption of continuity of prevention, treatment and peer-support programs for common conditions among PWID, such as HCV infection, and other consequences, including a significant decrease in harm reduction interventions [12, 13]. Due to all these factors, most countries have fallen behind in their stated objectives to eliminate HCV infection by 2030. In many countries, there has actually been an increase in HCV transmission, especially in vulnerable populations, such as drug users.

It is clear that the HCV pandemic transcends drug users and extends well beyond this group. However, it remains a priority population that must be addressed in a focused manner. Thus, it is crucial to fully understand the barriers to HCV diagnosis and treatment in drug users, design and evaluate interventions and implement evidence informed programs as quickly, effectively and broadly as possible.

2. Successful models of care

Drug users are often not engaged in medical care in the traditional sense or in the usual way. Doing so will require innovation, imagination, and flexibility. Programs will also need to be rigorous and evaluable, such that they can be continuously made more pertinent and effective. Fortunately, there have been a number of successful interventions in many countries and regions from which we can all learn.

2.1 Australia

Since July 2017, in Australia, physicians Matt Young and Joss O’Loan, together with nurse Mim O’Flynn and phlebotomist Mick Mooney, are carrying on a mobile outreach project called the “Kombi Clinic” [14]. The medical personnel don Hawaiian shirts, drives around the greater Brisbane area in an older VW Kombi van fitted with a mobile clinic, bringing life-saving information, and offering free HCV testing and access to treatment where they think they might find people in need of care. The aim of this unique and, many say entertaining, project is to destigmatize HCV infection, by breaking down social barriers, and simplify the access to HCV treatment, thus bringing the offer of cure to the patients rather than expecting them to seek care in the usual way. During the first visit, a doctor provides pre-test counseling and collects medical and social information. Then, a blood test for the diagnosis and evaluation of HCV, HBV and HIV is performed, together with a FibroScan test to assess liver scarring. All participants receive a 10–20 AUD supermarket voucher. On the following visit, performed by telehealth or in person at the next Kombi Clinic, patients found to be productively infected with HCV can actually initiate antiviral therapy. The service is generally accessed by 20–30 clients per week, mainly people who use drugs, people receiving opiate substitution therapy, people experiencing homelessness, indigenous people, people who are, or have been, incarcerated and people living with HIV. The initiative is focused on HCV, but broader health services can be provided, if required. During the period from 2017 to 2020, 25 locations were visited: hostels (22%), homeless drop-in centres (20%), drug rehabilitation services (16%), public festivals (13%) and community centres (12%). A total of 1280 high-risk patients were screened, of whom 453 tested positive for HCV antibodies and 282 were found to be viremic. Of these, 236 were further engaged in care and started HCV treatment. Although 79 were lost to follow up, 103/105 (98%) in whom an outcome was determined are cured. It is quite clear that for these 103 individuals, HCV treatment and cure would never have been achieved without the Kombi Clinic. The challenge for this program going forward is to reduce the rate of loss to follow up so that even more people can benefit from this unique and highly productive initiative.

2.2 Scotland

Professor John Dillon of the University of Dundee has established a program to eliminate HCV (including among all drug users) from the Tayside region of Scotland by 2025. By 2020, his multidisciplinary team had diagnosed 90% of infected individuals patients and treated 80% of this total, already meeting the WHO target for HCV elimination a decade early. In 2017, the National Health Service had launched a trial of “Treatment as Prevention” (TasP), by scaling up HCV outreach and treatment among drug users [15]. The rationale was to use broad-based treatment to lower HCV prevalence among PWIDs to reduce the rate of new infections and re-infections in this population that was, in large part, fueling the pandemic. The key-points of this model were: “keep it local”, so patients had to travel as little as possible to achieve a cure of HCV infection; “keep it simple”, eliminating any unnecessary tests, assessments, and clinic/hospital appointments; and “keep it known”, namely try to deliver the care through someone they already know and trust (including their pharmacist), as that makes it even easier to reach those needing therapy. The programme was carried out in a variety of community-based locations, including conventional clinical settings, drug treatment centres, needle exchange locations, community pharmacies, nurse-led outreach clinics and prisons. In each location, testing, pre-treatment assessment, and treatment were all provided. The only evaluation requiring travel was liver ultrasound assessment, only needed in those with advanced disease. During treatment scaleup (January 2017 to April 2020), 713 courses of HCV treatment were initiated and were completed in 630 (88.4%) cases. Cure was formally demonstrated in 577 (91.6%) cases. Longer term follow-up after cure was maintained such that 39 cases of reinfection were documented. Re-treatment was completed in 21 cases, with 17 individuals achieving a cure once again. This program is more comprehensive than that of the Kombi Clinic, allowing for the initiation of a larger number of courses of treatment in a variety of community-based settings. Maintenance of engagement in care after cure allowed for the diagnosis of re-infection in a more effective way, and successful retreatment in a number of cases. Here again, an appreciable number of participants (over 10%) did not complete HCV treatment, a group that could likely be re-engaged in care in this structured program going forward.

2.3 Iceland

In 2016, Iceland initiated TraP HepC, a nationwide HCV elimination program. By adopting innovative strategies, the goals for HCV elimination (diagnosing and treating 90% and 80% of infections, respectively) were achieved within a remarkable 3 years [16, 17]. Iceland took advantage of its central registries for infectious diseases, its low threshold for treating addiction, and its national healthcare system to maximize diagnosis, identify potential patients and make treatment access easy for everyone. The program was based on a multidisciplinary approach: nationwide awareness campaigns were promoted, access to testing was improved and harm reduction services were scaled up simultaneously. The priority was given to drug users, but every adult who had chronic HCV infection could participate.

Patients were identified using cross-referencing of four different data sources and, to reach out to those who may be at risk of infection but remained undiagnosed, information was shared through web pages, social media and leaflets, which were sent to every home in the country. The initial evaluation and ongoing care were mainly performed in one of the two involved hospitals, but testing and treatment were provided by staff members through outreach in prisons, homeless shelters and other locations as deemed necessary. To optimize adherence of drug users to treatment, many strategies were implemented, including on-treatment monitoring, pill boxes, increased nurse counseling and support, linkage to other relevant health services (e.g. addiction treatment, psychiatric services), travel stipends for those living outside the city and economic incentives, such as prepaid mobile phone cards. The first visit was comprehensive: review of full medical and social history; completion of all relevant laboratory work; and evaluation of liver fibrosis. Qualified patients started antiviral therapy within 2–4 weeks. Between February 2016 and February 2019, 865 cases were confirmed and 824 were linked to care. Treatment was initiated in 795 cases, with 717 (90.1%) documented cures. This all-of-country approach is particularly impressive, with a unique ability to address the issue of loss to follow up in an effective way.

2.4 United States

In Baltimore, a different, innovative approach was conceived, relying on a peer-based recruitment strategy [18]. An initial group of HCV antibody-positive drug users were interviewed as “primary indexes” to obtain demographic and drug use information and data about their drug use network. Primary indices were educated on HCV infection, disease and treatment, and then encouraged to recruit other drug users from their network and promote linkage to care. Individuals who presented for engagement (with coupons given to them by their recruiters redeemed for a small financial incentive) were screened by medical staff and, if matching the description and fulfilling all the eligibility criteria, they became secondary indexes and could proceed with treatment and recruitment of their own network. Overall, 17 of 36 primary indexes were able to recruit at least one network member. Of the 64 members recruited, 62 became secondary indexes. Of these, 19 were able to recruit at least one network member. Among all the recruited individuals, 69 participants had chronic HCV infection and were not previously linked to care. Of these, 31 scheduled an appointment, 14 started HCV treatment and 8 completed the therapy. The main barriers for participants that did not schedule an appointment were general health care access and the insurance requirement of a referral from a primary care provider to see an HCV specialist. This program demonstrates the power of peers. If this was included within broader initiatives to address the significant barriers to engagement that were identified, its true benefit could be more fully realized.

2.5 Europe

Four countries (Ireland, United Kingdom, Romania and Spain) are involved in the HepCare project [19, 20]. The aims of this program are to develop, implement and evaluate several interventions to improve HCV diagnosis and treatment among vulnerable populations. The testing and treatment interventions are site-specific, based on the needs of the target populations. Peer support and community- and prison-based treatment are also provided. The HepCare project includes many targeted interventions:

HepCheck, based on a point-of-care testing strategy through services in the community (opiate agonist therapy clinics, homeless services, prisons). For those testing positive and previously untreated, formal work-up and referrals are offered. Any barriers to treatment are identified and addressed by health professionals and community service staff.

HepLink aimed to improve linkage to care among those receiving opiate agonist therapy. A trained HCV nurse conducts a full on site work up and facilitates treatment referrals.

HepFriend, designed to develop and implement peer support interventions within the HepCheck and HepLink work packages. Peers, namely people who with lived experience of HCV infection, drug abuse, and/or homelessness, are recruited and trained to give support within their communities and the specialized services, contributing to integration in HCV care. Peers are also trained to assist the clinical staff in the HepCheck and HepLink activities.

HepEd, aimed at teaching and delivering educational interventions to vulnerable communities and preparing healthcare providers to collaborate in a shared primary/secondary partnership for HCV treatment.

Overall, 2608 participants were recruited across 218 sites in four European cities (Dublin, London, Bucharest and Sevilla) and HCV antibody test results were obtained for 2568, 1074 (41.8%) of which were positive. Of 687 viremic individuals, 319 (43.5%) began treatment. To date, among those in whom an outcome has been ascertained, 196/211 (92.3%) are cured. Participants interviewed at all sites said that HepCare improved their HCV treatment experience by decreasing waiting times, giving assistance during the care journey, and providing services in non-traditional locations more suitable to their complex lifestyles. This heroic multicentre approach highlights the benefit of flexible, collaborative and individualized partnerships for HCV elimination. The active inclusion of trained peers further strengthens trust and collaboration between vulnerable people and healthcare providers. In addition, educational interventions help to make affected communities more aware of HCV infection and its possible consequences and the availability of curative treatment.

The strategies discussed above (summarized in Table 1) do not represent all those attempted and implemented around the world to address HCV infection among drug users. In some cases, they have led to the elimination of HCV infection from entire countries or regions. In others, they illustrate novel initiatives that, if applied more broadly and incorporated more formally within health care delivery programs, will be important components of HCV elimination. There is clearly a need to be actively present within the vulnerable communities, with low-barrier access to testing (including point of care testing) suitable to the drug using population. It is also essential to provide those with viremic infection prompt engagement in care and access to antiviral therapy. Building a strong collaboration with the drug using community based on trust and a perceived capability to understand and address needs other than HCV care will also be a key factor in HCV eradication.

Model (location)	Strategy	Results	Advantages
Kombi Clinic (Australia)	Circulating van fitted with a mobile clinic Free testing and rapid access to HCV treatment Other health care needs addressed	1280 patients screened 453 HCV Ab+ 282 HCV RNA+ 236 treatment starts 103/105 cured to date	Receptive environment to remove social barriers Mobile program bringing treatment to the patients
Treatment as Prevention (TasP) (Tayside, Scotland)	Keep it local Keep it simple Keep it known	713 treatment starts 577/630 cured to date	Simplification of work-up and access to treatment broad, multidisciplinary community-based approach
TraP HepC (Iceland)	Coordinated national program Priority given to drug users Large media campaign	865 viremic individuals identified 795 treatment starts 717 cured to date	National approach with broad community support Effective and integrated approach to drug users
Peer-based recruitment strategy (Baltimore, USA)	Identification of cases through HCV-infected peers	69 viremic individuals identified 14 treatment starts 8 completed therapy	Community-based approach Recognition of the importance of peers in programs aimed at recruiting drug users into HCV care
HepCare project (Ireland, United Kingdom, Romania, Spain)	Multiple strategies adapted to local needs and priorities; HepCheck (testing) HepLink (linkage to care) HepFriend (peer support) HepEd (education to vulnerable communities and healthcare providers)	2568 patients screened 1074 HCV Ab+ 687 HCV RNA+ 319 treatment starts 196/211 cured to date	Ambitious approach adapted to multiple and varied local circumstances Recognition of importance of peers and educational interventions

Table 1.

Comparison of the main HCV elimination strategies attempted in different Countries worldwide.

3. The Vancouver model

3.1 Current scenario and challenges

We have known for some years that the prevalence of HCV infection within Vancouver’s inner city (including the Downtown East Side or DTES) exceeds 60%, particularly among active drug users. Given this large burden of disease and potential for ongoing high-level transmission, understanding the barriers to progression through the care cascade is essential to optimize treatment strategies and enhance HCV care. Compared to the current situation, significant scale-up of treatment rates is required in order to decrease prevalence and have a meaningful impact on onward transmission.

Marginalization of people who use drugs in the DTES of Vancouver has led to their disengagement from health care, including HCV and HIV care. The shift from an individual physician-based approach to a multidisciplinary, community-based intervention may be an important strategy to address this issue. Indeed, many HCV-infected inner-city residents, who are actively using drugs, are facing other issues more challenging than their HCV infection: housing and financial insecurity, untreated mental illness, and active untreated addiction. In this context, an approach that targets their medical, social, psychological, and addiction-related needs, and one that focuses on engagement, multidisciplinary and durability are required to identify candidates for HCV treatment and provide them with antiviral therapy in a way that is accountable, generalizable and scalable. Several strategies have been proposed to identify HCV-infected inner-city residents, engage them in care, provide them with antiviral therapy, establish conditions to maximize treatment completion and the achievement of cure. Despite the improvements in linkage to diagnosis and investigations to treatment, in our city of Vancouver, initiation of treatment and, even more, completion of HCV therapy for this population are still critical, especially in light of a significant opioid crisis with 7 overdose deaths/day, largely among individuals disengaged from care.

3.2 Operationalizing an innovative, multidisciplinary approach – the community pop-up clinic (CPC)

It is in this context that we have developed our highly successful Community Pop-Up Clinic (CPC) model aimed at reducing barriers to treatment and maximizing HCV therapy initiation in the inner-city population. In weekly events held at various inner-city locations (mainly single room occupancy housing projects, each with 30–90 residents on average), we interact with up to 30 residents/event. If HCV infection is present (determined by review of provincial records or ascertained by point-of-care testing offered on site), immediate engagement in care is offered. This will address social, psychiatric, medical, and addiction-related needs and deliver HCV therapy in this context. During the CPC event, an immediate consultation with a nurse or doctor is offered, with follow-up within the week at our centrally located clinic, with prompt initiation of HCV therapy in this context focused on achieving and maintaining engagement, ensuring that it is both multidisciplinary and durable, according to individual need. If someone does not attend the follow-up appointment, we would implement short-term strategies, such as return visits to the place of residence using our medical van (with subsequent provision of HCV treatment at a distance) or alternate strategies for follow up.

In summary, the program developed at our Vancouver Infectious Diseases Centre (VIDC) provides ongoing, long-term access to specialty medical care and support services in order to target the clinical, psychological, and social factors along with addiction-related needs that impact drug users, particularly the population from the DTES.

From January 2021 to November 2022 (23 months), we conducted 80 CPCs and evaluated 1440 individuals. Of these, 477 individuals (33.1%) were found to carry HCV antibodies, with 331 (69.4%) found to be viremic. We attempted to engage all in broad-based care to treat their HCV infection. To date, engagement has been secured in 289 (87.3%) cases (Figure 1). At this time, 252 have started treatment and one individual died of an opioid overdose in the pre-treatment phase. Of these, 11 remain on treatment, only 3 have been lost to follow-up and one additional individual succumbed to an opioid overdose. Of the 237 who have completed treatment, a definitive outcome has been ascertained in 219 cases, with 216 cures, 2 virologic relapses and one early reinfection. The effective cure rate among the 224 individuals in whom a definite outcome has been established is 96.4% (216/224). It is worth noting that in this vulnerable population where 7 opioid overdose deaths/day in the community, we only documented 2 overdose deaths in our cohort.

Figure 1.

Cascade of care – Community Pop-Up Clinic (CPC) Program (2021–2022). Through our CPC model, from January 2021 to November 2022, we effectively engaged in treatment 289 subjects. HCV cure was confirmed in 216 cases out of 224 (96.4%) in whom a definite outcome has been established.

The classical cascade of care (Figure 2) of HCV diagnosis and treatment has been defined according to four specific parameters:

1. Initial engagement.

2. Treatment preparation.

3. Treatment phase.

4. HCV cure confirmation.

Figure 2.

Classic cascade of care. The classic cascade of care involved 4 consecutive phases, each of them involving further specific steps.

Thinking of our program as one that means to identify viremic individuals (many of whom have been diagnosed in the remote past), a conceptual re-definition of the cascade may allow us to define and monitor a more meaningful measure of its success. Thinking of the steps to cure HCV infection from the initial interaction at a CPC event, the cascade becomes (Figure 3):

1. Time from initial engagement to treatment initiation.

2. Initiation and completion of antiviral therapy.

3. Ascertainment of treatment outcome.

Figure 3.

“Care to cure (C2C)” initiative. The “Care to cure (C2C)” initiative represents a simplified model of cascade of care elaborated by understanding the critical steps of the traditional strategy in order to allow a greater engagement and treatment of PWIDs.

This functional cascade would allow us to evaluate another aspect of program performance, as a more efficient progression towards cure would likely serve to increase the strength of engagement and allow for more individuals to be treated over time. The duration of treatment is a fixed number of weeks, most usually 8–12 weeks. Current data seems to suggest that the absence of viremia as soon as 4 weeks after the end of treatment almost always predicts cure. Programs such as ours are ideally designed to maintain individuals in care once therapy has started and following its completion. Our data shows a loss to follow-up rate of 1–2%, which supports this assertion. The variable on which we can act is the progression from initial contact to treatment initiation. In the cohort presented above, the median time was 6 weeks. This needs to be maintained or improved going forward, and this will be a key priority for us in the coming years.

Taken together, the data we present validates the development of multidisciplinary programs, such as ours aimed at treating HCV in vulnerable populations that must be engaged in care for HCV elimination to become a reality and documents additional societal benefits that could be achieved from such a program. This is a highly successful initiative on several fronts. The majority of individuals would not have received HCV treatment without this initiative, with many having had documented viremia several years before. The high success rate of therapy shows that, if treatment is delivered within a system appropriate for the specific patients, it can be as successful as has been demonstrated in clinical trials, but in a much more challenging population. In addition, our very low rate of loss to follow-up shows our success in the process of engagement strategies.

However, our program does have certain limitations. Some patients remain untreated. After we have determined that they are viremic and eligible for treatment, in some cases we are unable to proceed. The structure and size of our program are such that comprehensive follow-up may not always be possible, especially if the individual’s status has changed. This prolongs the time from care (our knowledge that an individual is viremic) to treatment and reduces our ability to eliminate HCV in this key population.

4. Conclusion

When it was initially put forward in 2016, the goal of viral hepatitis elimination (including HCV infection) over the next decade and a half seemed both aspirational and attainable. As we are now halfway between 2016 and 2030, it appears to be more daunting than we could have imagined. Of course, there has been a pandemic that has affected our ability to set up and maintain effective programs. Despite this, we can report a number of success stories in many parts of the world, including innovative approaches to drug-using populations. However, such programs have been largely driven by local champions and adapted to local needs. To our minds, there remains the need to develop, implement and evaluate strategies that are community-based and provide HCV treatment in a broader context, where all the needs of the individual that is before us are met in a coordinated fashion. The initial goal of such programs must be engagement in care and first meet the priority needs of the population, that include management of addiction in the context of an opioid overdose crisis, in our community and in many others in the developed world. The programs must be accountable, both to the community we serve and to public health authorities and other funding agencies. They must be subjective to rigorous evaluation, to celebrate their successes and identify challenges that must be addressed to improve their impact and effectiveness. They must also be scalable, to address the needs of all PWIDs and vulnerable groups throughout the world. Elimination of HCV infection must be viewed as a partnership between those who provide care and those who receive it. Partnership with inner city populations is particularly complex but attainable. If we do the right things in the right way at the right time, we will not only eliminate HCV, but improve the health and well-being of the most vulnerable among us and contribute in a significant way to improve society as a whole. There is no higher calling.

Acknowledgments

The authors wish to thank Atira Housing and its chief operating officer, Janice Abbott, for their partnership in the implementation of our Community Pop-up Clinic program. We also wish to acknowledge our lead peer worker, John Callander, for his fearless work in liaising our program with the community in a compassionate and effective manner. Finally, we wish to recognize all the residents of the Downtown East Side of Vancouver who have allowed us to partner with them in a way that has made us all better people.

Conflicts of interest

Dr. Conway has received research grants, honoraria and/or acted as a remunerated advisor for AbbVie, Astra Zeneca, Gilead Sciences, GSK, Indivior Canada, Merck, Moderna, Sanofi Pasteur, Seqirus, and ViiV Healthcare. In particular, AbbVie and Gilead Sciences have funded the Community Pop-up Clinic program in a direct way.