Increasing national trend of direct-acting antiviral discontinuation among people treated for HCV 2016–2021

Abstract

Background: Direct-acting antiviral (DAA) treatment discontinuation may negatively impact HCV elimination efforts. In Australia, DAA therapy is pharmacy dispensed, generally in 4-week amounts, with the approved duration (8–24 wk) and volume dispensed reported in pharmaceutical administrative data. This analysis assessed national HCV treatment discontinuation. Methods: Individuals commencing DAAs between 2016 and 2021 were assessed for treatment discontinuation. Individuals with a single dispensation of their entire treatment course were excluded. Treatment discontinuation was defined as ≥4 weeks of approved treatment duration not dispensed. Factors associated with treatment discontinuation were assessed using Cox regression. Factors associated with retreatment following treatment discontinuation were assessed using logistic regression. Results: Of 95,275 individuals who were treated, 88,986 were included in the analysis of whom 7532 (9%) discontinued treatment. Treatment discontinuation increased from 6% in the first half of 2016 to 15% in 2021. Longer treatment durations (vs. 8 wk) were associated with increased discontinuation risk (12 wk: adjusted HR = 3.23; 95% CI: 2.90, 3.59; p < 0.001, 16–24 wk: adjusted HR = 6.29; 95% CI: 5.55, 7.14; p < 0.001). Of individuals discontinuing treatment, 24% were retreated. Early discontinuation (4 wk treatment dispensed) increased the likelihood of retreatment (adjusted OR = 3.91; 95% CI: 3.44, 4.44; p < 0.001). Those with early discontinuation of glecaprevir/pibrentasvir 8 weeks (vs. sofosbuvir/velpatasvir 12 wk) had a lower likelihood of retreatment (adjusted OR = 0.62; 95% CI: 0.49, 0.79; p < 0.001). Initial treatment discontinuation was associated with an increased risk of retreatment discontinuation (adjusted HR = 4.41; 3.85, 5.05; p < 0.001). Conclusions: DAA treatment discontinuation increased over time corresponding to increasing treatment uptake through primary care among people who inject drugs. The use of simplified, short-duration therapies may reduce treatment discontinuation. Access to adherence support and retreatment will be essential for HCV elimination.

Adherence in Hepatitis C Virus Treatment: What We Know

“…An Australian study assessed trends of DAA discontinuations and HCV retreatment at the national level. 44 Data on treatment and retreatment were collected from administrative records provided by the Australian Pharmaceutical Benefit Scheme (PBS). For the PBS analysis, treatment discontinuation was defined as “1 or more repeat authorized prescription courses (28 [day] supply) not dispensed”; early discontinuation was defined as “discontinuing after the first 28 days of the treatment course had been dispensed”; late discontinuation was defined as “discontinuing after 56 days or more had been dispensed”; and retreatment was defined as “the commencement of a different DAA regimen any time after the end of the initial treatment date or the same DAA regimen ≥28 days after the last dispensation of the initial treatment.” Among 88,986 patients infected with HCV, 9% discontinued DAA treatment.…”

“…46 47 Furthermore, Carson et al demonstrated that short-duration therapies may promote fewer treatment discontinuations. 44 It is important to identify poor adherence and consider using more “forgiving” medications when optimal adherence appears unlikely. 46 In practice, strategies to improve adherence should vary based on the patient population and factors that contribute to lower SVR rates.…”