Direct-acting antivirals (DAAs) cure hepatitis C, but a person can get hepatitis C again if they are exposed to the virus. This is called reinfection. Reinfections are a reality of hepatitis C work. CATIE talked to three people with expertise in hepatitis C reinfection and asked them to share their perspectives and experience related to working with people with hepatitis C reinfections, why it’s important for us to reframe our thinking about reinfections, and policy-related considerations.
- Professor Gregory Dore is the head of the Viral Hepatitis Clinical Research Program at the Kirby Institute located in the University of New South Wales (UNSW) in Sydney, Australia
- Bernadette Lettner is a hepatitis C treatment nurse with the Toronto Community Hep C Program
- Sofia Bartlett is a senior scientist for sexually transmitted and blood-borne infections (STBBIs) at the BC Centre for Disease Control and an adjunct professor in the School of Population and Public Health, University of British Columbia
See more in the article: Hepatitis C reinfection: Risks, realties and responses
Professor Gregory Dore, head, Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW Sydney
What perspectives on hepatitis C reinfection have you heard in recent years and how have views evolved over time with more data about reinfection in the DAA era of hepatitis C treatment?
Initially, hepatitis C reinfection, or more accurately the prospect of reinfection, was used by many clinicians as a reason not to provide treatment to people who inject drugs. This attitude was prevalent in the interferon era of hepatitis C treatment and continued into the current DAA era, particularly driven by the high pricing of DAA treatment in many settings.
Attitudes toward whether potential reinfection should be used to restrict hepatitis C treatment have clearly changed in recent years, probably for several reasons. First, national and international efforts focused on hepatitis C elimination have highlighted the importance of treatment access for people who inject drugs and other priority populations. Second, cost-effectiveness analyses have clearly demonstrated that treatment for people who inject drugs is highly cost-effective, even when reinfection is factored in. Third, there has been strong leadership from academic, clinical and community representatives to promote the fundamental right of access to hepatitis C treatment for people who inject drugs, including retreatment for reinfection. Finally, some key countries have provided strong evidence of the impact of equitable access and high-level uptake of hepatitis C treatment among people who inject drugs. For example, from the commencement of the Australian government-funded hepatitis C treatment program in 2016 there was no restriction on access to treatment based on drug use and there was no limit on the number of treatment courses an individual could receive. This policy has led to a reduction in the prevalence of hepatitis C infection among people who inject drugs in Australia from more than 50% in 2015 to 17% in 2020–2021.
What can hepatitis C reinfection rates tell us about elimination efforts and hepatitis C services?
Hepatitis C reinfection is not evidence of poor elimination efforts, but rather often the reverse. In the early DAA period of hepatitis C treatment, settings that were seeing more reinfection cases were generally treating more people who inject drugs. Seeing hepatitis C reinfections signified that people who inject drugs had access to treatment. Thus, reinfection can be viewed as a barometer of hepatitis C treatment provision.
This is not to downplay the importance of access to primary prevention through high-coverage needle and syringe provision and ready availability of opioid agonist treatment (OAT). But, even in settings with high-coverage harm reduction, many cases of hepatitis C reinfection have been observed. The response to hepatitis C reinfection should include optimizing individual harm reduction access, monitoring for reinfection with regular testing for current infection, early diagnosis and access to retreatment.
High numbers of hepatitis C reinfection cases are inevitable in the early stages of broad elimination efforts in settings where a large population has ongoing risk of exposure. As elimination efforts progress and the prevalence of hepatitis C infection declines among populations of people who inject drugs, the number of reinfection cases should also decline. In Australia, we are already seeing this occur and expect further declines over the coming years. One caveat is that there continue to be large numbers of reinfection cases within the prison setting in Australia, given more limited harm reduction access within the prison setting than the community setting. This includes poorer access to OAT, although this is improving, and no access at all to needle syringe programs. Hepatitis C elimination efforts would clearly be enhanced if this situation was altered so that the prison setting maintained the community standard of primary prevention including high-coverage OAT and needle and syringe distribution.
There is no doubt that hepatitis C elimination efforts would be further enhanced through equitable access to both hepatitis C treatment and primary prevention, in keeping with key health and human rights principles.
Bernadette Lettner, hepatitis C treatment nurse, Toronto Community Hep C Program
As a hepatitis C treatment nurse, what has been your experience with hepatitis C reinfections in your clinical practice?
As with any highly contagious virus, infections — and reinfections — do occur. I’m really happy when someone approaches me, identifying that they have a potential re-exposure risk and requesting hepatitis C viral load testing. This shows a high level of knowledge, personal engagement in health and trust in hepatitis C treatment.
When you are caring for someone who has a hepatitis C reinfection, do you do anything differently than when you care for someone with a primary hepatitis C infection?
From a clinical perspective, we are lucky that retreatment for hepatitis C looks exactly the same as a primary course of treatment. First-line treatments are used to treat any hepatitis C infection (primary infection and reinfection) that has not been treated before. In the case of a reinfection, first-line treatments are used because the individual has been treated previously for a different virus, but the current virus is treatment naïve.
Sometimes, there is confusion between treatment for reinfection and retreatment for people where the first course of medication didn’t work. In the case of retreatment, which is rarely necessary given the high cure rates, the virus has been exposed to a course of medication, but the medication has not cured the individual of hepatitis C. When this happens, additional factors must be considered to determine which treatment to use to increase the likelihood of curing the virus with a second course of medication. This sometimes includes using a different combination of medications, sometimes referred to as salvage therapy.
Even though the medication and response to treatment in reinfection is clinically no different than for primary infection, I have seen other differences in the treatment of hepatitis C reinfection. There are limitations on medication coverage in both the private and public payer systems for treating reinfection that do not exist when treating someone for a primary infection. There is also a corresponding increase in judgment and stigma surrounding reinfection. I think there is a tendency to blame or hold responsible individuals when we look at the circumstances involved in re-exposure to and reinfection with hepatitis C, while ignoring system-level factors. If someone is unable to access harm reduction supplies because programs are only open 9 a.m. to 5 p.m. Monday to Friday, that is a system failure. Drug use does not keep office hours. If one person can access treatment for hepatitis C, but their partner can’t, that is a system failure. As a clinician working with people who have hepatitis C, and someone who has experience in this field, I truly believe it is my responsibility to ensure those system-level inequities and drivers of infection are addressed while also offering appropriate hepatitis C medication to treat an infection.
Universal hepatitis C treatment coverage for all patients in Canada is required, including coverage for retreatment when reinfection occurs. Universal access also means that people who are unemployed, newcomers to Canada and people in the prison system all have access to uninterrupted treatment and hepatitis C care.
There are times, if someone is open to having the conversation with me, that we talk about how re-exposure and reinfection occur. This is really more a learning for me, and I am thankful when people are open to sharing intimate details of their drug use with me. It helps to inform the harm reduction education I can provide and address gaps in the system. Drugs, and the way people use them, change. People who use drugs are experts and have valuable information to share; by paying attention to this knowledge, we become better at treating and preventing hepatitis C.
Sofia Bartlett, senior scientist, STIBBIs, BC Centre for Disease Control, and adjunct professor, School of Population and Public Health, University of British Columbia
What can you tell us about current public reimbursement policies across Canada for treatment for hepatitis C reinfection?
All publicly funded drug plans in Canada include DAA therapies on their formulary for treatment of chronic hepatitis C infection. While some plans require that a substantial amount of documentation be submitted with requests for reimbursement of DAAs, none of them have restrictions on eligibility for treatment, provided patients meet the overall criteria to be covered by the plan. Clinical guidelines in the United States, Australia and Europe all recommend people with hepatitis C virus reinfection initiate DAA therapy promptly, as this is cost-effective and also reduces occurrence of onward hepatitis C transmission. Despite this, the majority of Canadian publicly funded drug plans do not guarantee they will approve reimbursement of DAAs for hepatitis C reinfection. In a recent study, we found that 6% (1/16) of publicly funded drug plans in Canada will not approve reimbursement of DAAs for hepatitis C reinfection at all, and an additional 50% will only consider reimbursement on a case-by-case basis, with no criteria published to explain what might lead to denial of a DAA reimbursement request. Only 44% of publicly funded drug plans in Canada confirmed that they definitely cover reimbursement of DAAs for people with hepatitis C reinfection. While 60% of Canadians have private health insurance with drug coverage, usually as a benefit of employment, people affected by hepatitis C are much less likely to have private health insurance. Therefore, policies and criteria for reimbursement of DAAs through publicly funded drug plans play a critical role in creating or removing barriers to accessing hepatitis C treatment in Canada. If people with hepatitis C reinfection are denied reimbursement of DAAs through publicly funded drug plans, they may not be able to access this potentially life-saving treatment at all.
The lack of clarity about criteria for denial of DAA reimbursement requests for people with hepatitis C reinfection may contribute to prescribers having the perception that people living with hepatitis C infection have only one chance for reimbursement of DAAs to be approved on publicly funded plans in Canada. This may lead to delaying initial DAA treatment, particularly among groups that are viewed as having an elevated risk of hepatitis C reinfection, such as people who inject drugs. Delaying initial hepatitis C treatment or denying reimbursement of treatment for people with hepatitis C reinfection could result in significant adverse outcomes, both at the individual and population levels. These include preventable morbidity and mortality because of liver disease and extrahepatic manifestations of chronic hepatitis C infection, as well as onward hepatitis C transmission, undermining efforts to eliminate hepatitis C infection in Canada.
What kinds of public reimbursement policies for hepatitis C reinfection would you like to see implemented across Canada?
Current policies followed by publicly funded drug plans in Canada place the burden of responsibility on individuals to protect themselves from hepatitis C reinfection. These policies ignore the fact that access to things that allow people to protect themselves from hepatitis C reinfection, such as harm reduction, housing, adequate levels of income and healthcare, is inequitable in Canada. To address these inequities, publicly funded drug plans in Canada should apply the same criteria that are applied to initial DAA reimbursement requests to subsequent requests for treatment of hepatitis C reinfection. There should be no difference in how publicly funded drug plans adjudicate requests for reimbursement of DAAs for people with initial hepatitis C infection compared with subsequent hepatitis C infections.
Hepatitis C reinfection is a public health issue and should be responded to by utilizing evidence-based policies and interventions. These can include referral to harm reduction programs or providing integrated care that addresses other unmet needs, such as support to access housing, income assistance or mental healthcare. It is understandable that publicly funded drug plans have concerns about costs associated with potentially needing to cover multiple DAA treatment courses for hepatitis C reinfections. However, this issue cannot be mitigated by restricting patient access to potentially life-saving treatments. It requires collaboration between health system and community stakeholders to ensure that the ideal suite of programs and services that will allow individuals to protect themselves from hepatitis C infection are available equitably across Canada.
Related resources
Snell G, Marshall AD, van Gennip J et al. Public reimbursement policies in Canada for direct-acting antiviral treatment of hepatitis C virus infection: A descriptive study. Canadian Liver Journal. 2023, 6(2): 190-200. Available from: https://canlivj.utpjournals.press/doi/full/10.3138/canlivj-2022-0040