Modeling based response guided therapy in subjects with recent hepatitis C infection

Evan Gorstein, Marianne Martinello, Alexander Churkin, Swikriti Dasgupta, Kevin Walsh, Tanya L. Applegate, David Yardeni, Ohad Etzion, Susan L. Uprichard, Danny Barash, Scott J. Cotler, Gail V. Matthews, Harel Dahari

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish
Article number104862
JournalAntiviral Research
Volume180
DOIs
StatePublished - 1 Aug 2020

Keywords

  • Direct-acting antivirals
  • Hepatitis c virus
  • Mathematical modeling
  • Recent infection

ASJC Scopus subject areas

  • Pharmacology
  • Virology

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