Mathematical/Computational Virology & Medicine
Modeling based response guided therapy in subjects with recent hepatitis C infection
Evan Gorstein, Marianne Martinello, Alexander Churkin, Swikriti Dasgupta, Kevin Walsh, Tanya Applegate, David Yardeni, Ohad Etzion, Susan L. Uprichard, Danny Barash, Scott J. Cotler, Gail V. Matthews, Harel Dahari
BACKGROUND & AIMS:
Mathematical modeling of viral kinetics has been shown to identify patients with chronic hepatitis C virus (HCV) infection who could be cured with a shorter duration of direct-acting antiviral (DAA) treatment. However, modeling therapy duration has yet to be evaluated in recently infected patients. The aim of this study was to retrospectively examine whether modeling can predict outcomes of six-week sofosbuvir (SOF) and weight-based ribavirin (R) therapy in patients with recent HCV infection.
Modeling was used to estimate viral host parameters and to predict time to cure for 12 adults with recent HCV infection (<12 months of infection) who received six weeks of treatment with SOF+R.
Modeling results yielded a 100% negative predictive value for SOF+R treatment failure in eight patients and suggested that a median of 13 [interquartile range:12-17] weeks of therapy would be required for these patients to achieve cure. Modeling predicted cure after six and five weeks of therapy in the two participants who achieved a sustained virological response. Cure was predicted after five weeks of therapy in one patient who relapsed following treatment.
The results suggest that a modeling-based response-guided approach might help identify individuals with recent HCV who will be appropriate for treatment with ultra-short duration potent DAA therapy. Prospective real-time modeling under current DAA regimens is needed to validate the potential of response-guided therapy in the management of recent HCV infection.