Eight weeks of sofosbuvir/velpatasvir for genotype 3 hepatitis C in previously untreated patients with significant (F2/3) fibrosis

Abstract

Summary Twelve weeks sofosbuvir/velpatasvir (SOF/VEL) is a highly effective pan‐genotypic regimen for hepatitis C. Phase 2 data suggest 8 weeks of treatment may be sufficient for previously untreated noncirrhotic patients with genotype 3 (GT3) infection. To maximize the number of patients potentially cured within a fixed treatment budget, we elected to treat such patients locally eligible for treatment (F2/3), with 8 weeks of SOF/VEL. By local protocol, treatment‐naive patients with F2 (LSM > 6.9kPa < 9.5kPa) or F3 fibrosis (≥9.5kPa < 12.5kPa) were eligible for 8‐week SOF/VEL treatment. Patients commencing treatment before 1 Oct 2017 were identified from the Scottish HCV database. Baseline and treatment outcome data obtained. Ninety patients were included for analysis (72 (80%) male, mean age 45 (IQR ± 8.4), 28 (31.1%) F3 fibrosis). Opioid agonist therapy (OAT) was prescribed in 82 (91.1%) patients. Of 49 patients attending Glasgow city Alcohol and Drug Services, 27 (55.1%) had evidence of recent drug use (< 3 months) including 8 (16.3%) with self‐reported intravenous drug use. On an intention‐to‐treat basis, SVR rates were 86/90 (95.6%, 95% CI 89.0‐98.8). Excluding those who prematurely discontinued treatment (n = 4), died prior to SVR testing (n = 1) or whom experienced reinfection (n = 1), per‐protocol SVR rate was 84/84 (100%, 95% CI 95.7‐100.0). In conclusion, eight‐week SOF/VEL is highly effective in treatment‐naive GT3 patients with significant fibrosis. This offers a non‐protease inhibitor‐based 8‐week regimen which may be useful for complex drug interactions or where time‐limited opportunity for treatment. In limited resource settings, reduction in drug acquisition costs may help achieve progress towards the goal of HCV elimination.

Efficacy of ultra-short, response-guided sofosbuvir and daclatasvir therapy for Hepatitis C: a single arm mechanistic pilot study

“…This dose adjustment was subsequently deemed unnecessary once drug-interaction data emerged, such that this study is likely to underestimate the efficacy of 8 weeks SOF/DCV. More recent studies corroborate our finding of >90% cure with 8 weeks NS5A/NS5A inhibitor combination 39,49,50 . Larger trials are warranted to evaluate 8 weeks SOF/DCV therapy for patients with mild liver disease (irrespective of speed of virological response).…”

Efficacy of ultra-short, response-guided sofosbuvir and daclatasvir therapy for hepatitis C in a single-arm mechanistic pilot study

“…This dose adjustment was subsequently deemed unnecessary once drug-interaction data emerged, such that this study is likely to underestimate the efficacy of 8-week SOF/DCV. More recent studies corroborate our finding of >90% cure with 8 weeks NS5A/NS5A inhibitor combination ( Yakoot et al, 2017 ; El-Shabrawi et al, 2018 ; Boyle et al, 2020 ). Larger trials are warranted to evaluate 8-week SOF/DCV therapy for patients with mild liver disease (irrespective of speed of virological response).…”

Directly observed therapy at opioid substitution facilities using sofosbuvir/velpatasvir results in excellent SVR12 rates in PWIDs at high risk for non-adherence to DAA therapy

“…SOF/VEL is a fixed-dose combination tablet of sofosbuvir, an inhibitor of the NS5B RNA polymerase blocking viral replication, and velpatasvir, which inhibits the NS5A protein required for the assembly and release of viral particles. SOF/VEL proved to be safe and showed SVR12 rates close to 100% in previous studies [ 36 – 38 ]. Since the removal of reimbursement restrictions concerning HCV treatment in Europe, access to DAA including SOF/VEL has been simplified for all patients [ 39 ].…”