Real‐world outcomes of unrestricted direct‐acting antiviral treatment for hepatitis C in Australia: The South Australian statewide experience

Abstract

In March 2016, the Australian government offered unrestricted access to direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) to the entire population. This included prescription by any medical practitioner in consultation with specialists until sufficient experience was attained. We sought to determine the outcomes and experience over the first twelve months for the entire state of South Australia. We performed a prospective, observational study following outcomes of all treatments associated with the state's four main tertiary centres. A total of 1909 subjects initiating DAA therapy were included, representing an estimated 90% of all treatments in the state. Overall, SVR12 was 80.4% in all subjects intended for treatment and 95.7% in those completing treatment and follow-up. 14.2% were lost to follow-up (LTFU) and did not complete SVR12 testing. LTFU was independently associated with community treatment via remote consultation (OR 1.50, 95% CI 1.04-2.18, P = .03), prison-based treatment (OR 2.02, 95% CI 1.08-3.79, P = .03) and younger age (OR 0.98, 95% CI 0.97-0.99, P = .05). Of the 1534 subjects completing treatment and follow-up, decreased likelihood of SVR12 was associated with genotype 2 (OR 0.23, 95% CI 0.07-0.74, P = .01) and genotype 3 (OR 0.23, 95% CI 0.12-0.43, P ≤ .01). A significant decrease in treatment initiation was observed over the twelve-month period in conjunction with a shift from hospital to community-based treatment. Our findings support the high responses observed in clinical trials; however, a significant gap exists in SVR12 in our real-world cohort due to LTFU. A declining treatment initiation rate and shift to community-based treatment highlight the need to explore additional strategies to identify, treat and follow-up remaining patients in order to achieve elimination targets.

Facilitating treatment of HCV in primary care in regional Australia: closing the access gap

“…This is consistent with the notion of ‘warehousing’ where patients had already been assessed for treatment and were waiting for DAA therapy to become available 17. We were able to show an increase in prescribing in the most recent months, the majority of which were in primary care.…”

“…Rates of loss to follow-up and therefore incomplete SVR data have previously been shown to be higher in this group 16. This is likely due to the higher prevalence of active injecting drug use, younger age and lower prevalence of advanced liver disease in primary care cohorts 17. Strategies such as early follow-up between end of treatment and SVR in addition to incentives are being explored 18…”

Loss to follow‐up: A significant barrier in the treatment cascade with direct‐acting therapies

“…Despite the rapid advances in DAA treatments and their high effectiveness, LTF remains a significant barrier in the HCV treatment cascade and could impact the overall effectiveness of treatment. In this study, the overall LTF rate of 10% was lower than the rates reported in a real‐world study conducted in South Australia among GT1‐ and GT4‐infected individuals (14.2%) and in Egypt among GT4‐infected patients (29%) . However, our findings indicate that: 1) LTF, including death, exceeds viral failure with HCV DAA therapy and requires considerable attention in the HCV elimination pathway; and 2) LTF rates vary significantly by genotype and treatment regimen.…”

“…Third, as the assessment of factors contributing to SVR and LTF rates (eg IDU, cirrhosis) were based on diagnostic codes, misclassification of these variables is possible (Table ). As ‘homelessness’ status was not available in our data, the potential association between this variable and LTF could not be measured . For LTF assessment, due to the low power, multivariable models could only be conducted for the overall and LDV/SOF ± RBV treatment regimen.…”

“…Although DAAs have removed barriers related to longer treatment duration and poor tolerability, data from real‐world settings on loss to follow‐up (LTF) and premature discontinuation of DAA therapies are very limited. While newer DAAs are highly efficacious, LTF could blunt the overall real‐world effectiveness . Thus, characterizing LTF and its predictors is important towards achieving World Health Organization (WHO) elimination goals …”