An Open-Label, Randomized, Active-Controlled Trial of 8 Versus 12 Weeks of Elbasvir/Grazoprevir for Treatment-Naive Patients with Chronic Hepatitis C Genotype 1b Infection and Mild Fibrosis (EGALITE Study): Impact of Baseline Viral Loads and NS5A Resistance-Associated Substitutions
Journal
Journal of Infectious Diseases
Journal Volume
221
Journal Issue
2
Pages
557-566
Date Issued
2020
Author(s)
Huang C.-F.
Hung C.-H.
Cheng P.-N.
Bair M.-J.
Huang Y.-H.
Lee P.-L.
Chen J.-J.
Chien R.-N.
Peng C.-Y.
Lin C.-Y.
Hsieh T.-Y.
Cheng C.-H.
Dai C.-Y.
Huang J.-F.
Chuang W.-L.
Yu M.-L.
Abstract
Background: A 12-week grazoprevir/elbasvir regimen is highly effective against hepatitis C virus genotype 1 (HCV-1) infection. The efficacy of an 8-week regimen for treatment-naive HCV-1-infected patients with mild fibrosis has not been determined. Methods: Treatment-naive HCV-1b-infected patients with mild fibrosis were randomly assigned to receive 8 (n = 41) or 12 (n = 41) weeks of grazoprevir/elbasvir therapy. The primary end point was a sustained virologic response, defined as an HCV RNA level of < 12 IU/mL, at posttreatment week 12 (SVR12). Results: SVR12 was achieved by 87.8% of patients (36 of 41) in the 8-week arm and 100% (41 of 41) in the 8-week arm of the full-analysis population and by 90.0% (36 of 40) and 100% (41 of 41), respectively, in the per-protocol population (all P =. 055). In the 8-week arm, a significantly lower SVR12 rate was observed among patients with a high HCV-1b load, defined as ?1 500 000 IU/mL (79% vs 100%; P =. 042), and among those with a baseline Y93H resistance-associated substitution (RAS) frequency of >15% in HCV nonstructural protein 5A (NS5A; 40.0% vs 97.1%; P =. 004). Between-group analysis demonstrated that, among patient with a high HCV-1b load and a baseline Y93H RAS frequency of >15%, those in the 8-week arm had a substantially lower SVR12 rate than those in the 12-week arm (40.0% vs 100.0%). All 4 HCV-1b relapses had a Y93H RAS frequency of >99% at posttreatment week 12. Conclusions: Twelve weeks of grazoprevir/elbasvir therapy is highly effective for treatment-naive patients with mild fibrosis. A truncated, 8-week grazoprevir/elbasvir regimen might be applied for those with low viral loads or without a significant NS5A RAS frequency. ? 2019 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
Subjects
abbreviated; CHC; DAA; elbasvir; grazoprevir; treatment
SDGs
Other Subjects
alanine aminotransferase; bilirubin; elbasvir plus grazoprevir; nonstructural protein 5A; antivirus agent; benzofuran derivative; elbasvir-grazoprevir drug combination; imidazole derivative; quinoxaline derivative; adult; aged; alanine aminotransferase blood level; anemia; antiviral resistance; Article; bilirubin blood level; chronic hepatitis C; cohort analysis; controlled study; dizziness; drug safety; fatigue; female; gastrointestinal symptom; headache; Hepatitis C virus subtype 1b; human; liver fibrosis; major clinical study; male; middle aged; nausea; priority journal; pruritus; randomized controlled trial; resistance associated substitution; side effect; sustained virologic response; therapy effect; treatment duration; virus load; chronic hepatitis C; complication; drug combination; drug effect; genetics; genotype; Hepacivirus; immunology; liver cirrhosis; virology; Adult; Aged; Antiviral Agents; Benzofurans; Drug Combinations; Drug Resistance, Viral; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Imidazoles; Liver Cirrhosis; Middle Aged; Quinoxalines; Sustained Virologic Response; Viral Load
Publisher
Oxford University Press
Type
journal article