@article{92e362eb9efc4f4a872b37c0d68442b5,
title = "Modeling based response guided therapy in subjects with recent hepatitis C infection",
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.",
keywords = "Direct-acting antivirals, Hepatitis c virus, Mathematical modeling, Recent infection",
author = "Evan Gorstein and Marianne Martinello and Alexander Churkin and Swikriti Dasgupta and Kevin Walsh and Applegate, {Tanya L.} and David Yardeni and Ohad Etzion and Uprichard, {Susan L.} and Danny Barash and Cotler, {Scott J.} and Matthews, {Gail V.} and Harel Dahari",
note = "Funding Information: GVM advises, is on the speakers' bureau, and received grants from Gilead . She is on the speakers{\textquoteright} bureau and received grants from AbbVie and Bristol-Myers Squibb . She received grants from Janssen. HD has consulted for CoCrystal Inc. None of the other authors has any financial interest or conflict of interest related to this research. Funding Information: The study was supported in part by U.S. NIH grants R01AI078881 and R01GM121600. The Kirby Institute is funded by the Australian Government Department of Health and Ageing. The clinical research reported in the previous DARE C II publication was supported by Gilead Sciences Inc. as an investigator-initiated study. The funders had no role in current study design, data collection and analysis, decision to publish, or preparation of the manuscript.GVM advises, is on the speakers' bureau, and received grants from Gilead. She is on the speakers? bureau and received grants from AbbVie and Bristol-Myers Squibb. She received grants from Janssen. HD has consulted for CoCrystal Inc. None of the other authors has any financial interest or conflict of interest related to this research. Funding Information: The study was supported in part by U.S. NIH grants R01AI078881 and R01GM121600 . The Kirby Institute is funded by the Australian Government Department of Health and Ageing. The clinical research reported in the previous DARE C II publication was supported by Gilead Sciences Inc. as an investigator-initiated study. The funders had no role in current study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2020 Elsevier B.V.",
year = "2020",
month = aug,
day = "1",
doi = "10.1016/j.antiviral.2020.104862",
language = "English",
volume = "180",
journal = "Antiviral Research",
issn = "0166-3542",
publisher = "Elsevier",
}
