The advent of oral directly acting antivirals heralds a new era in hepatitis C virus (HCV) management in which elimination is a realistic goal.1 A crucial element of the elimination strategy is the regular screening of at-risk populations. The undiagnosed HCV population not only represents a significant burden of disease but also drives transmission. A major challenge associated with screening is the loss to follow-up that occurs with people who inject drugs (PWID). This is compounded by the multiple steps inherent to conventional testing. A positive HCV antibody screen requires subsequent HCV RNA testing to distinguish active from resolved infection. In practice, this means that at least 3 clinic visits are necessary before treatment can begin.
A recent mathematical modelling study published in the Journal of Viral Hepatitis addresses the question of HCV testing frequency in PWID.2 The model assessed settings with differing HCV prevalence rates: low, medium, and high (25%, 50%, 75%, respectively). The model assumed universal access to treatment with 100% initiation after 30 days of diagnosis and a 95% cure rate. The output was the testing frequency required to achieve the World Health Organization (WHO) target of 80% reduction in incidence by 2030 (using 2015 as a baseline). The impact of changing to a testing strategy where HCV RNA or a novel HCV core antigen test is used directly was also evaluated. This would allow skipping of the initial HCV antibody test, reducing loss to follow-up and lag in diagnosis.
The model results show that in low-prevalence PWID populations, it is possible to achieve the 80% reduction target with a 2-yearly testing strategy. However, this result is based on an initial HCV antibody test with a 100% follow-up of HCV RNA testing within 3 months and an 80% testing coverage. Interestingly, if the testing were increased to 6-monthly the target could be reached as early as 2024. For medium-prevalence PWID populations, annual testing is required to reach the target if there is 90% coverage and 50% follow-up with HCV RNA testing.
Finally, for high-prevalence PWID populations (typical for the United States and France) 3-monthly testing using the HCV antibody test would achieve only a 60% incidence reduction assuming 100% follow-up to further testing and 80% coverage. Changing to a direct HCV RNA/HCV core antigen testing strategy adds a small improvement but even with 90% coverage the target will not be met. Other prevention measures such as needle and syringe programs and opioid substitution therapy3 will need to be expanded to achieve the 80% incidence reduction.
This study highlights the significance of initial prevalence for HCV elimination strategies in PWID populations. More frequent testing, improved linkage to care, and greater testing coverage will all be important in the path to elimination.
Infectious Disease Advisor talked to Dr Nick Scott from the Department of Epidemiology and Preventive Medicine, Monash University, Australia, and the Disease Elimination Program, Burnet Institute, Melbourne, Australia, lead author of the previously discussed mathematical modelling study published in the Journal of Viral Hepatitis.
Infectious Disease Advisor: For clinicians, what are the main implications of your study in high, medium and low HCV prevalence populations?
Dr Scott: The main implication for clinicians is that regular HCV tests and HCV education should be offered to people who indicate that they are actively injecting drugs. In low-, medium- and high-prevalence settings it would be appropriate to offer 2-yearly, annual, and 6-monthly tests, respectively.
In particular, the study demonstrates that many of the public health benefits of HCV treatment will not be realized without clinicians actively following up antibody-positive patients for confirmatory RNA testing and treatment commencement.
Infectious Disease Advisor: Are these recommendations likely to change over time if HCV prevalence decreases?
Dr Scott: These recommendations are likely to remain until HCV has been controlled as a public health threat, which could take up to 2030 in many settings. Beyond this, further modelling will be required to inform updates to testing guidelines.
Infectious Disease Advisor: Do you think it is inevitable that to meet the WHO HCV elimination there will need to be large-scale roll-out of HCV RNA core antigen testing in place of HCV antibody testing?
Dr Scott: The models suggest that in settings with low HCV prevalence, existing testing methods (ie, hepatitis C antibody testing followed by confirmatory RNA testing) are likely to be sufficient to meet the hepatitis C elimination target, provided a high coverage of testing can be achieved among risk populations. However, for settings of moderate to high prevalence, the availability of hepatitis C RNA core antigen testing would make reaching the targets considerably more feasible.
HCV elimination within the timeframe envisaged by the WHO will require considerable focus on PWID particularly in countries, such as the United States, where prevalence is very high. In combination with expanded access to treatment, novel testing approaches will likely be important.
- World Health Organization. Combating hepatitis B and C to reach elimination by 2030. Advocacy Brief. http://www.who.int/hepatitis/publications/hep-elimination-by-2030-brief/en/. May 2016. Accessed September 12, 2018
- Scott N, Sacks-Davis R, Pedrana A, Doyle J, Thompson A, Hellard M. Eliminating hepatitis C: the importance of frequent testing of people who inject drugs in high-prevalence settings [published online July 26, 2018]. J Viral Hepat. doi: 10.1111/jvh.12975
- Martin NK, Boerekamps A, Hill AM, Rijnders BJA. Is hepatitis C virus elimination possible among people living with HIV and what will it take to achieve it? J Int AIDS Soc. 2018;21 Suppl 2:e25062.