BACKGROUND: The standard of care for HCV genotype 1 is a protease inhibitor (telaprevir or boceprevir) combined with pegylated interferon (PEG-IFN) and ribavirin (RBV). A lead-in phase of PEG-IFN/RBV therapy before addition of the protease inhibitor has been used, with the aim of improving response rates by reducing the development of protease inhibitor resistance. However, whether such a strategy can bring benefit to patients is unclear. METHODS: A viral dynamic model was used to compare in silico HCV dynamics in patients treated with a period of PEG-IFN/RBV lead-in therapy followed by the addition of a protease inhibitor versus immediate triple therapy without lead-in. RESULTS: The model predicts that both regimens result in a similar end-of-treatment viral load change (viral decline or breakthrough). Thus, the current lead-in strategy may not decrease the rate of viral breakthrough/relapse or increase the rate of sustained virological response. This agrees with available data from clinical trials of several HCV protease inhibitors, such as telaprevir, boceprevir and faldaprevir. CONCLUSIONS: These results suggest that current PEG-IFN/RBV lead-in strategies may not improve treatment outcomes. However, viral kinetics during a period of PEG-IFN/RBV therapy, combined with other factors, such as the IL28B polymorphism and baseline viral load, can identify IFN-sensitive patients and help develop response-guided therapies.
BACKGROUND: The standard of care for HCV genotype 1 is a protease inhibitor (telaprevir or boceprevir) combined with pegylated interferon (PEG-IFN) and ribavirin (RBV). A lead-in phase of PEG-IFN/RBV therapy before addition of the protease inhibitor has been used, with the aim of improving response rates by reducing the development of protease inhibitor resistance. However, whether such a strategy can bring benefit to patients is unclear. METHODS: A viral dynamic model was used to compare in silico HCV dynamics in patients treated with a period of PEG-IFN/RBV lead-in therapy followed by the addition of a protease inhibitor versus immediate triple therapy without lead-in. RESULTS: The model predicts that both regimens result in a similar end-of-treatment viral load change (viral decline or breakthrough). Thus, the current lead-in strategy may not decrease the rate of viral breakthrough/relapse or increase the rate of sustained virological response. This agrees with available data from clinical trials of several HCV protease inhibitors, such as telaprevir, boceprevir and faldaprevir. CONCLUSIONS: These results suggest that current PEG-IFN/RBV lead-in strategies may not improve treatment outcomes. However, viral kinetics during a period of PEG-IFN/RBV therapy, combined with other factors, such as the IL28B polymorphism and baseline viral load, can identify IFN-sensitive patients and help develop response-guided therapies.
Authors: Kui Li; Eileen Foy; Josephine C Ferreon; Mitsuyasu Nakamura; Allan C M Ferreon; Masanori Ikeda; Stuart C Ray; Michael Gale; Stanley M Lemon Journal: Proc Natl Acad Sci U S A Date: 2005-02-14 Impact factor: 11.205
Authors: Alexander J Thompson; Andrew J Muir; Mark S Sulkowski; Dongliang Ge; Jacques Fellay; Kevin V Shianna; Thomas Urban; Nezam H Afdhal; Ira M Jacobson; Rafael Esteban; Fred Poordad; Eric J Lawitz; Jonathan McCone; Mitchell L Shiffman; Greg W Galler; William M Lee; Robert Reindollar; John W King; Paul Y Kwo; Reem H Ghalib; Bradley Freilich; Lisa M Nyberg; Stefan Zeuzem; Thierry Poynard; David M Vock; Karen S Pieper; Keyur Patel; Hans L Tillmann; Stephanie Noviello; Kenneth Koury; Lisa D Pedicone; Clifford A Brass; Janice K Albrecht; David B Goldstein; John G McHutchison Journal: Gastroenterology Date: 2010-04-24 Impact factor: 22.682
Authors: Eileen Foy; Kui Li; Chunfu Wang; Rhea Sumpter; Masanori Ikeda; Stanley M Lemon; Michael Gale Journal: Science Date: 2003-04-17 Impact factor: 47.728
Authors: Christoph Sarrazin; Tara L Kieffer; Doug Bartels; Brian Hanzelka; Ute Müh; Martin Welker; Dennis Wincheringer; Yi Zhou; Hui-May Chu; Chao Lin; Christine Weegink; Henk Reesink; Stefan Zeuzem; Ann D Kwong Journal: Gastroenterology Date: 2007-02-21 Impact factor: 22.682
Authors: Michael W Fried; Mitchell L Shiffman; K Rajender Reddy; Coleman Smith; George Marinos; Fernando L Gonçales; Dieter Häussinger; Moises Diago; Giampiero Carosi; Daniel Dhumeaux; Antonio Craxi; Amy Lin; Joseph Hoffman; Jian Yu Journal: N Engl J Med Date: 2002-09-26 Impact factor: 91.245