Treatment of Hepatitis C with An Interferon-Based Lead-In Phase: A Perspective from Mathematical Modelling

Abstract

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. 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. 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. 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.