Treatment of hepatitis C with an interferon-based lead-in phase: a perspective from mathematical modelling. Journal Article

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Authors: Rong, L; Guedj, J; Dahari, H; Perelson, AS
Article Title: Treatment of hepatitis C with an interferon-based lead-in phase: a perspective from mathematical modelling.
Abstract: 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.
Journal Title: Antiviral Therapy
ISSN: 2040-2058; 1359-6535
Publisher: Unknown  
Date Published: 2014