Direct-acting Antiviral Therapy and Reinfection Among People With Chronic Hepatitis C Virus Infection and Recent Injecting Drug Use in Community-based Settings: the SHARP-C Study

In Australia, hepatitis C virus (HCV)-related morbidity and mortality have doubled in the past decade, with health care costs of $220 million per annum1. This is due to a large, ageing population with chronic infection (230,000), and low uptake of existing interferon-based therapy (1-2% per year) due to side-effects, and sub-optimal therapy efficacy. The majority of new (90%) and existing (80%) cases of HCV infection occur among people who inject drugs (PWID).

In the community, 15-20% of current PWID report recent (last month) receptive needle/syringe sharing2. Qualitative research shows that decisions about sharing equipment are multi-factorial and can include issues ranging from service access (such as distance to service and opening hours), concerns about anonymity, perceptions that HCV is ubiquitous and unavoidable3 to socially-located concerns that promote use of sterile equipment such as a desire to avoid "track marks"4. There is no research that examines sharing of injecting equipment in those with successful therapy in either community or prison settings.

Increasing access to HCV therapy is a key objective of national and NSW Hepatitis C Strategies5,6. The advent of well-tolerated, simple, oral hepatitis C virus (HCV) regimens - direct acting antivirals (DAAs) - has the potential to transform this landscape. These are much shorter, tolerable treatment regimens with cure >95%, providing an opportunity to reverse the rising burden of advanced liver disease. From 1st March 2016, these highly efficacious HCV therapies have been listed on the Pharmaceutical Benefit Scheme, and people with recent injecting drug use are eligible to receive them. This is an important feature of the listing. In many countries, people who have not ceased injecting drug use are ineligible to receive DAA therapy7, despite the fact that they comprise a significant proportion of HCV cases. Australia is therefore poised to lead the world in the scale-up of new therapies to an extent that many countries with such exclusions will not be able to achieve.

This feature of DAA access also affords unique opportunities with respect to the implementation of treatment scale-up in community drug treatment clinics. Australia has good treatment coverage for people who are opioid dependent, with over 50% of opioid dependent people estimated to engage in opioid substitution therapy (OST) 8. Community-based drug treatment clinics represent another logical venue for expansion of HCV care beyond existing tertiary HCV treatment centres 9,10.

Although response to DAA HCV therapy is high, lower responses have been observed among people with previous treatment experience9, cirrhosis9 and those with baseline or emergent resistance associated variants10. Such resistance associated variants can persist for up to two years after treatment11, affect re-treatment options12, and be transmitted to new hosts13. Further, PWID are likely to be exposed to multiple HCV infections as a result of ongoing high-risk behaviours and might commonly harbour mixed HCV infections (infection with two or more distinct viruses) 14. Underlying mixed HCV infection can contribute to nonresponse during therapy14, which has implications for DAA regimens that are preferentially active against specific viral genotypes or subtypes. These data argue for surveillance of HCV resistance and mixed HCV infection among PWID to resolve residual concerns regarding their clinical and public health significance.