Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 62, Issue 2, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.02217-17
Keywords
HCV; NS5A inhibitor; glecaprevir; pibrentasvir; protease inhibitors
Categories
Funding
- AbbVie
- AbbVie GK
- MSD KK
- Dainippon Sumitomo Pharma Co. Ltd.
- Bristol-Myers Squibb
- Gilead
- Dainippon Sumitomo Pharma
- Mitsubishi Tanabe Pharma Corporation
- Chugai Pharmaceutical Co.
- Toray Industries Inc.
- Takeda Pharmaceutical Company
- Ajinomoto
- Astellas
- AstraZeneca
- Eisai
- GlaxoSmithKline
- Janssen
- Kowa
- Kyorin
- MSD
- Nippon Kayaku
- Nippon Seiyaku
- Nippon Shinyaku
- Roche
- Teijin
- Torii
- Tsumura
- Zeria
- Daiichi Sankyo
- Bayer
- GlaxoSmithKline KK
- Chugai Pharmaceutical Co. Ltd.
- Meiji Seika
- Otsuka Pharmaceutical Co. Ltd.
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Glecaprevir and pibrentasvir are hepatitis C virus (HCV) pangenotypic inhibitors targeting NS3/4A protease and NS5A, respectively. This once-daily, fixed-dose combination regimen demonstrated high sustained virologic response 12 weeks postdosing (SVR12) rates in CERTAIN-1 and CERTAIN-2 studies in Japanese HCV-infected patients, with a low virologic failure rate (1.2%). There were no virologic failures among direct-acting antiviral (DAA)-treatment-naive genotype 1a (GT1a) (n = 4)-, GT1b (n = 128)-, and GT2 (n = 97)-infected noncirrhotic patients treated for 8 weeks or among GT1b (n = 38)-or GT2 (n = 20)-infected patients with compensated cirrhosis treated for 12 weeks. Two of 33 DAA-experienced and 2 of 12 GT3-infected patients treated for 12 weeks experienced virologic failure. Pooled resistance analysis, grouped by HCV subtype, treatment duration, prior treatment experience, and cirrhosis status, was conducted. Among DAA-naive GT1b-infected patients, the baseline prevalence of NS3-D168E was 1.2%, that of NS5A-L31M was 3.6%, and that of NS5A-Y93H was 17.6%. Baseline polymorphisms in NS3 or NS5A were less prevalent in GT2, with the exception of the common L/M31 polymorphism in NS5A. Among DAA-experienced GT1b-infected patients (30/32 daclatasvir plus asunaprevir-experienced patients), the baseline prevalence of NS3-D168E/T/V was 48.4%, that of NS5A-L31F/I/M/V was 81.3%, that of the NS5A P32deletion was 6.3%, and that of NS5A-Y93H was 59.4%. Common baseline polymorphisms in NS3 and/or NS5A had no impact on treatment outcomes in GT1-and GT2-infected patients; the impact on GT3-infected patients could not be assessed due to the enrollment of patients infected with diverse subtypes and the limited number of patients. The glecaprevir-pibrentasvir combination regimen allows a simplified treatment option without the need for HCV subtyping or baseline resistance testing for DAA-naive GT1-or GT2-infected patients. (The CERTAIN-1 and CERTAIN-2 studies have been registered at ClinicalTrials. gov under identifiers NCT02707952 and NCT02723084, respectively.)
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