BACKGROUND: Telaprevir (TVR) is a hepatitis C virus (HCV) NS3.4A protease inhibitor that has exhibited antiviral activity in patients with HCV genotype 1 infection. The viral dynamics in patients dosed with TVR were compared with those reported for patients treated with interferon (IFN). METHODS: The dynamics of wild-type HCV genotype 1 in patients dosed with TVR monotherapy (n=36) and TVR plus pegylated interferon (PEG-IFN)-alpha2a (n=8) were quantified using a biphasic viral dynamic model. RESULTS: Patients dosed with either TVR monotherapy or TVR plus PEG-IFN-alpha2a had median first and second phase decreases of 12 per day and 1.1 per day, respectively. The second phase decrease was approximately 10-fold higher than reported values for IFN-based treatments (P<0.0001). Patients dosed with TVR plus PEG-IFN-alpha2a had a median remaining viral production after blockage (1-epsilon) of -2.37 log(10). In patients dosed with TVR monotherapy, increased TVR dosage of the same schedule was related to better blockage. CONCLUSIONS: These results suggested that TVR-based regimens for chronic HCV infection will lead to an early and more rapid viral decrease that could potentially result in higher sustained viral response rates as well as offer the potential for a reduced duration of treatment.
BACKGROUND:Telaprevir (TVR) is a hepatitis C virus (HCV) NS3.4A protease inhibitor that has exhibited antiviral activity in patients with HCV genotype 1 infection. The viral dynamics in patients dosed with TVR were compared with those reported for patients treated with interferon (IFN). METHODS: The dynamics of wild-type HCV genotype 1 in patients dosed with TVR monotherapy (n=36) and TVR plus pegylated interferon (PEG-IFN)-alpha2a (n=8) were quantified using a biphasic viral dynamic model. RESULTS:Patients dosed with either TVR monotherapy or TVR plus PEG-IFN-alpha2a had median first and second phase decreases of 12 per day and 1.1 per day, respectively. The second phase decrease was approximately 10-fold higher than reported values for IFN-based treatments (P<0.0001). Patients dosed with TVR plus PEG-IFN-alpha2a had a median remaining viral production after blockage (1-epsilon) of -2.37 log(10). In patients dosed with TVR monotherapy, increased TVR dosage of the same schedule was related to better blockage. CONCLUSIONS: These results suggested that TVR-based regimens for chronic HCV infection will lead to an early and more rapid viral decrease that could potentially result in higher sustained viral response rates as well as offer the potential for a reduced duration of treatment.
Authors: Harel Dahari; Evaldo S Affonso de Araujo; Bart L Haagmans; Thomas J Layden; Scott J Cotler; Antonio A Barone; Avidan U Neumann Journal: J Hepatol Date: 2010-05-27 Impact factor: 25.083
Authors: Bambang S Adiwijaya; Eva Herrmann; Brian Hare; Tara Kieffer; Chao Lin; Ann D Kwong; Varun Garg; John C R Randle; Christoph Sarrazin; Stefan Zeuzem; Paul R Caron Journal: PLoS Comput Biol Date: 2010-04-15 Impact factor: 4.475
Authors: Warren N Schmidt; David R Nelson; Jean-Michel Pawlotsky; Kenneth E Sherman; David L Thomas; Raymond T Chung Journal: Clin Gastroenterol Hepatol Date: 2013-07-18 Impact factor: 11.382