Evan Gorstein1, Marianne Martinello2, Alexander Churkin3, Swikriti Dasgupta1, Kevin Walsh1, Tanya L Applegate2, David Yardeni4, Ohad Etzion4, Susan L Uprichard1, Danny Barash5, Scott J Cotler1, Gail V Matthews2, Harel Dahari6. 1. The Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL, 60053, USA. 2. Kirby Institute, University of New South Wales, Sydney, NSW, Australia. 3. Department of Software Engineering, Sami Shamoon College of Engineering, Beer-Sheva, Israel. 4. Soroka University Medical Center, Beer Sheva, Israel. 5. Department of Computer Science, Ben-Gurion University of the Negev, Beer-Sheva, Israel. 6. The Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Medical Center, Maywood, IL, 60053, USA. Electronic address: hdahari@luc.edu.
Abstract
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 individuals. 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 individuals with recent HCV infection. METHODS: 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. RESULTS: Modeling results yielded a 100% negative predictive value for SOF + R treatment response in nine participants and suggested that a median of 13 [interquartile range: 8-16] weeks of therapy would be required for these patients to achieve cure. Modeling predicted cure after 5 weeks of therapy in the only modeled participant who achieved a sustained virological response. However, cure was also predicted for two participants who relapsed following treatment. CONCLUSIONS: The modeling results confirm that longer than 6 weeks of SOF + R is needed to reach cure in individuals with recent HCV infection. Prospective real-time modeling under current potent DAA regimens is needed to validate the potential of response-guided therapy in the management of recent HCV infection.
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 individuals. 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 individuals with recent HCV infection. METHODS: 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. RESULTS: Modeling results yielded a 100% negative predictive value for SOF + R treatment response in nine participants and suggested that a median of 13 [interquartile range: 8-16] weeks of therapy would be required for these patients to achieve cure. Modeling predicted cure after 5 weeks of therapy in the only modeled participant who achieved a sustained virological response. However, cure was also predicted for two participants who relapsed following treatment. CONCLUSIONS: The modeling results confirm that longer than 6 weeks of SOF + R is needed to reach cure in individuals with recent HCV infection. Prospective real-time modeling under current potent DAA regimens is needed to validate the potential of response-guided therapy in the management of recent HCV infection.
Authors: Natasha K Martin; Alicia Thornton; Matthew Hickman; Caroline Sabin; Mark Nelson; Graham S Cooke; Thomas C S Martin; Valerie Delpech; Murad Ruf; Huw Price; Yusef Azad; Emma C Thomson; Peter Vickerman Journal: Clin Infect Dis Date: 2016-02-16 Impact factor: 9.079
Authors: Ashish Goyal; Alex Churkin; Danny Barash; Scott J Cotler; Amir Shlomai; Ohad Etzion; Harel Dahari Journal: Open Forum Infect Dis Date: 2022-03-22 Impact factor: 4.423