Faculty Opinions recommendation of Baseline Polymorphisms and Emergence of Drug Resistance in the NS3/4A Protease of Hepatitis C Virus Genotype 1 following Treatment with Faldaprevir and Pegylated Interferon Alpha 2a/Ribavirin in Phase 2 and Phase 3 Studies.

2015 ◽  
Author(s):  
Philip Rosenthal
Keyword(s):  
Drug Resistance ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Interferon Alpha ◽  
Pegylated Interferon ◽  
Phase 2 ◽  
Genotype 1 ◽  
Virus Genotype ◽  
Phase 3 ◽  
Pegylated Interferon Alpha

scholarly journals Baseline Polymorphisms and Emergence of Drug Resistance in the NS3/4A Protease of Hepatitis C Virus Genotype 1 following Treatment with Faldaprevir and Pegylated Interferon Alpha 2a/Ribavirin in Phase 2 and Phase 3 Studies

2015 ◽  
Vol 59 (10) ◽  
pp. 6017-6025 ◽  
Author(s):  
K. L. Berger ◽  
J. Scherer ◽  
M. Ranga ◽  
N. Sha ◽  
J. O. Stern ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Interferon Alpha ◽  
Sustained Virologic Response ◽  
Pegylated Interferon ◽  
Virologic Response ◽  
Phase 2 ◽  
Genotype 1 ◽  
Phase 3 ◽  
Pegylated Interferon Alpha

ABSTRACTAnalysis of data pooled from multiple phase 2 (SILEN-C1 to 3) and phase 3 studies (STARTVerso1 to 4) of the hepatitis C virus (HCV) nonstructural protein 3/4A (NS3/4A) protease inhibitor faldaprevir plus pegylated interferon alpha/ribavirin (PR) provides a comprehensive evaluation of baseline and treatment-emergent NS3/4A amino acid variants among HCV genotype-1 (GT-1)-infected patients. Pooled analyses of GT-1a and GT-1b NS3 population-based pretreatment sequences (n= 3,124) showed that faldaprevir resistance-associated variants (RAVs) at NS3 R155 and D168 were rare (<1%). No single, noncanonical NS3 protease or NS4A cofactor baseline polymorphism was associated with a reduced sustained virologic response (SVR) to faldaprevir plus PR, including Q80K. The GT-1b NS3 helicase polymorphism T344I was associated with reduced SVR to faldaprevir plus PR (P< 0.0001) but was not faldaprevir specific, as reduced SVR was also observed with placebo plus PR. Among patients who did not achieve SVR and had available NS3 population sequences (n= 507 GT-1a;n= 349 GT-1b), 94% of GT-1a and 83% of GT-1b encoded faldaprevir treatment-emergent RAVs. The predominant GT-1a RAV was R155K (88%), whereas GT-1b encoded D168 substitutions (78%) in which D168V was predominant (67%). The novel GT-1b NS3 S61L substitution emerged in 7% of virologic failures as a covariant with D168V, most often among the faldaprevir breakthroughs; S61L in combination with D168V had a minimal impact on faldaprevir susceptibility compared with that for D168V alone (1.5-fold differencein vitro). The median time to loss of D168 RAVs among GT-1b-infected patients who did not have a sustained virologic response at 12 weeks posttreatment (non-SVR12) after virologic failure was 5 months, which was shorter than the 14 months for R155 RAVs among GT-1a-infected non-SVR12 patients, suggesting that D168V is less fit than R155K in the absence of faldaprevir selective pressure.

Clinical efficacy of combination therapy with ME3738 and pegylated interferon-alpha-2a in patients with hepatitis C virus genotype 1

2013 ◽  
Vol 44 (4) ◽  
pp. 410-419 ◽  
Author(s):  
Toshiji Saibara ◽  
Nobuyuki Enomoto ◽  
Shuichi Kaneko ◽  
Kazuaki Chayama ◽  
Michio Sata ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Combination Therapy ◽  
Interferon Alpha ◽  
Clinical Efficacy ◽  
Pegylated Interferon ◽  
Genotype 1 ◽  
Virus Genotype ◽  
Pegylated Interferon Alpha

Effects of Smoking on Pegylated Interferon alpha 2a and First Generation Protease Inhibitor-based Antiviral Therapy in Naïve Patients Infected with Hepatitis C Virus Genotype 1

2016 ◽  
Vol 25 (1) ◽  
pp. 15-24 ◽  
Author(s):  
Tim Zimmermann ◽  
Dietrich Hueppe ◽  
Stefan Mauss ◽  
Peter Buggisch ◽  
Heike Pfeiffer-Vornkahl ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Therapy ◽  
Interferon Alpha ◽  
Virological Response ◽  
Sustained Viral Response ◽  
Pegylated Interferon ◽  
Genotype 1 ◽  
Pegylated Interferon Alpha ◽  
Viral Response

Background & Aims: Smoking has multiple effects on factors influencing hepatitis C and antiviral therapy, including lipid metabolism, fibrosis, platelet count and adherence aspects. The aim of this analysis was to determine the impact of smoking on hepatitis C virus antiviral therapy. Methods: Data of two cohorts of an observational multicenter study including therapy-naïve patients infected with genotype 1 hepatitis C virus (HCV) treated with dual antiviral therapy (n=7,796) with pegylated interferon alpha 2a in combination with ribavirin, or triple antiviral therapy (n=1,122) containing telaprevir or boceprevir, were analysed. Results: In the univariate matched pair analysis of dual antiviral therapy patients (n=584), smoking was significantly associated with lower sustained viral response rates (p=0.026, OR 0.69 CI: 0.50 – 0.96). The effect of smoking on sustained viral response remained significant (p=0.028, OR 0.67 CI: 0.47 – 0.96) in the multivariate analysis when adjusting for all other baseline parameters with a significant association in the univariate analysis, i.e. diabetes, fibrosis, body mass index, transaminases and baseline viral load. Under protease inhibitors the influence of smoking on virological response did not arise. Conclusions: Smoking has a negative impact on antiviral therapy in naïve patients infected with HCV genotype 1 independently of age, gender, history of drug use or alcoholic liver disease. The effects of smoking might be overcome by the new antiviral agents.Abbreviations: APRI: AST to platelet ratio index; DAA: direct antiviral agent; DT: dual antiviral therapy; EoTR: end of treatment response; RVR: rapid virological response; EVR: early virological response; HCV: hepatitis C virus; IFN: interferon alpha; MPA: Matched Pair Analysis; NS: non-smokers; PEG-IFN: pegylated interferon alpha 2a; PI: protease inhibitor; RBV: ribavirin; SAE: serious adverse event; SOC: standard of care; S: smokers; SVR: sustained viral response.    

Mutations in the interferon sensitivity-determining region of hepatitis C virus genotype 2a correlate with response to pegylated-interferon-alpha 2a monotherapy

2009 ◽  
Vol 81 (3) ◽  
pp. 459-466 ◽  
Author(s):  
Kazuhiko Hayashi ◽  
Yoshiaki Katano ◽  
Takashi Honda ◽  
Masatoshi Ishigami ◽  
Akihiro Itoh ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Interferon Alpha ◽  
Pegylated Interferon ◽  
Virus Genotype ◽  
Pegylated Interferon Alpha
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