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As Australian clinicians, policy makers and communities affected by hepatitis C march into a new era of widespread, accessible Direct Acting Antivirals (DAAs), Dr Joseph Doyle from Melbourne’s Royal Alfred Hospital gave a timely presentation about the feasibility of eliminating HIV/Hepatitis C Virus co-infection.
The global burden of Hepatitis C Virus (HCV) infection is massive at 115-130 million people. Australia shares a relatively small burden of these infections, with an estimated 230 000 people living with HCV. Globally, 2.2 million people are co-infected with both HCV and HIV. Between 7 and 10% of people living with HIV have HCV, with their odds of acquiring HCV six times that of the HIV-uninfected population.
As with HIV infection and the familiar 90-90-90 goal-posts, the WHO has set ambitious targets for viral hepatitis. By 2030, WHO aims to eliminate hepatitis C transmission, with 90% reductions in incidence, and 90% of those infected treated effectively. This is expected to prevent 7.1 million deaths between 2015 and 2030.
To achieve this, health policy makers must address specific gaps in:
- Access to care
- Treatment, and
To be maximally effective, testing must be sufficiently frequent among populations at risk. Early diagnosis and treatment scale up to the point where 80% of all new cases of HCV were treated has been modelled to drastically reduce HCV incidence. Testing must be available at little or no cost to consumers, and provide reliable results. In Australia, antibody screening assays are widely available in organized laboratories with excellent quality assurance. Gaps persist in the diagnosis and assessment of hepatitis C: the current requirement for Nucleic Acid Amplification Testing (NAAT), genotyping, and assessment for fibrosis each presents a barrier to treatment. Multiple visits are often required to plan effective antiviral therapy, and each step represents a risk for disengagement. Algorithms for laboratories to deploy reflex HCV Ag/RNA testing in the event of reactive antibody screens would be useful. When these factors are combined models suggest improvements in treatment uptake and reductions in HCV incidence.
For hepatitis C and HIV coinfection, injecting drug use plays a role in up to half of cases. In contrast to HCV mono-infection, sexual transmission is also important, particularly among HIV+ men who have sex with men (MSM). Modelling suggests that sexual behavioural change could dramatically reduce sexual transmission of HCV, but the challenges to implementing this in an era of reducing condom use are considerable. Linking testing and early diagnosis with harm minimisation is important, and in some cohorts results in reduction of IDU risk behaviour.
Rates of testing for HCV are currently good among people living with HIV. Victorian data suggest that PLWHIV are tested an average of 1.4 times each year. Consideration should be given to increasing the frequency of testing, but restriction of this to higher risk individuals seems prudent.
Access to care has significantly improved in Australia in 2016. PBS-subsidised DAA therapy became available in March 2016, and unnecessary restrictions on prescribing for able prescribers were lifted in November of the same year. Australia wisely and bravely avoided the temptation to impose restrictions to access DAAs based on fibrosis, alcohol consumption and ongoing drug use. These aspects have seen the proliferation of interferon-free treatment in Australia. Interdisciplinary collaborations that have embraced participation by hepatologists, infectious disease physicians, sexual health physicians, public health professionals, virologists, general practitioners, and community members have liberated hepatitis C treatments from hospital environments to the community where much wider, more acceptable, sustainable implementation can develop. The multidisciplinary Consensus Statement on hepatitis C treatment has been instrumental in facilitating community provision of hepatitis C treatment.
Effective antiviral treatment of hepatitis C is the cornerstone of hepatitis C elimination. Although the safety and efficacy of the current generations of DAAs have provided extraordinary advances in the treatment of HCV infection, further advances are needed. The development of well-tolerated, safe, efficacious, pangenotypic regimens that require increasingly less reliance on fibrosis status and previous treatment history would be beneficial.
Communities at risk of coinfection include people who inject drugs and men who have sex with men predominantly, but those born overseas in countries with hig prevalence of both infections should not be neglected.
Cost effectiveness of interferon-free DAAs is well-established for those with advanced liver disease, but the cost of treating those with early infection without fibrosis is well within Australia’s resources.
Harm reduction strategies around injecting and sexual behaviour are an important part of primary prevention, but also crucial in preventing reinfection after successful therapy. Treatment offers opportunities to collaborate with harm reduction agencies, and reinforce messages of risk minimisation.
Although no highly efficacious vaccine for hepatitis C has been developed, the public health role of partially effective vaccines should be considered. The role for such vaccines will depend on the degree to which prevalence is reduced. If treatment uptake is high enough to reduce the prevalence of HCV to very low levels, a partially effective vaccine is unlikely to be of benefit. In the setting of ongoing high prevalence, or of high reinfection rated, a partially effective vaccine may be of considerable benefit.
Just as the HIV Cascade from the Kirby Institute’s Annual Surveillance Report informs HIV public health practice, so does the HCV care cascade. Priot to the introduction od DAAs in the community, only 2000 people accessed treatment for HCV. The introduction of HCV DAAs saw 27 000 HCV-infected people being treated by the end of July 2016, representing 13% of all people with HCV infection in Australia. We are on track to providing treatment to 40 000 people by the end of 2016. This enormous scale up of treatment for hepatitis C is unprecedented, and is a globally important public health intervention.
Networking models for HCV acquisition among PWID are well-described. Higher connectedness to communities with high HCV prevalence of confirms intuition. The high level of connectedness to others with HCV suggests strategies for increasing effective uptake among networks. Similar strategies might be effective among sexual networks of MSM in whom HCV is prevalent. ‘Bringing your friends in’ is potentially effective for both PWID and MSM networks, suggesting a singular effective strategy for co-infected networks.
To meet the WHO targets regarding reduced transmission, modelling suggests Australia must treat 4 700 HCV-infected PWID annually. To meet WHO mortality targets, 5 600 HOV infected PWID must be treated annually according to modeling. Given the uptake of DAA treatment in its first year, Australia is on track for reducing both mortality and transmission targets. Costs for achieving this are estimated to be around $7 billion, but prudent deal-making on behalf of the federal government is likely to achieve thi results for substantially less cost.
Reducing HCV acquisition among PLWHIV requires an understanding of the complex environment in which HCV transmissions occur. Factors include rates of partner change, condom utilization, injecting behaviour, sexual dynamics that include group sex an use of sex toys, and concomitant partnerships. Agency-based modelling, which accounts for such complexity, suggests a greater efficacy in HCV incidence reduction than compartment based modelling, and supports the efficacy of providing treatment to those with high risk sexual or injecting networks.
How can this be implemented? The Co-EC Study examines the utility of nurse-facilitated hepatitis C treatment in community settings. This study demonstrated that most people aith coinfection can be treated safely and effectively in community settings, providing that collaborative care is available when needed.
In summary, there are many parallels between HIV and Hepatitis C treatment. Treatment cascades are informative for both conditions, and there are many primary and secondary prevention messages that can be shared with benfit between sexual and injecting risk networks. Australia is on track to eliminate hepatitis C and HIV coinfection with its insightful, innovative adoption of community-based direct acting antiviral treatments for hepatitis C.