Clinical–liver, pancreas, and biliary tractDynamic Hepatitis C Virus Genotypic and Phenotypic Changes in Patients Treated With the Protease Inhibitor Telaprevir
Section snippets
Patient Population and Study Design
Thirty-four patients were enrolled into a randomized, double-blind, placebo-controlled, 14-day, multiple-dose, phase 1b trial and received one of the following doses of telaprevir: 450 mg every 8 hours (10 patients), 750 mg every 8 hours (8 patients), 1250 mg every 12 hours (10 patients), or placebo (6 patients). The clinical results of the trial have been reported in detail elsewhere.21 All patients had a chronic infection with HCV subtype 1a/b with plasma HCV-RNA levels of 105 IU/mL or
Viral Response Pattern to Telaprevir
The samples analyzed in this study were obtained from 34 patients infected with HCV genotype 1 who were dosed for 14 days with placebo or telaprevir in a randomized, double-blind, phase 1b study.21 Of the 34 patients, 27 (79%) had failed prior treatment. As expected, patients who received placebo showed no significant change in their plasma HCV-RNA levels. All patients who received telaprevir had a sharp initial decline of approximately 3-log10 in plasma HCV-RNA concentration during the first 2
Discussion
The development of drug resistance has been a challenge for treatment strategies in many viral infections such as human immunodeficiency virus, hepatitis B virus, herpes simplex virus, and influenza.32 The high replication rate and the error-prone nature of viral RNA polymerases generate a viral quasispecies from which variants resistant to viral inhibitors can be selected. Minor populations of pre-existing, resistant variants have a fitness advantage over wild-type virus in the presence of a
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Cited by (0)
Supported in part by a grant from the Deutsche Forschungsgemeinschaft (KFO 129; Teilprojekt 2, to C.S. and S.Z.). T.L.K., D.B., B.H., U.M., Y.Z., H–M.C., C.L., and A.D.K. are employees of Vertex Pharmaceuticals. C.S. and S.Z. have financial arrangements with Vertex Pharmaceuticals and Schering-Plough Research Institute (Kenilworth, NJ) (consultancies, research support).
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C.S. and T.L.K. contributed equally to this work.