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A multiscale model of the action of a capsid assembly modulator for the treatment of chronic hepatitis B
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A multiscale model of the action of a capsid assembly modulator for the treatment of chronic hepatitis B
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Journal Article
A multiscale model of the action of a capsid assembly modulator for the treatment of chronic hepatitis B
2025
Overview
Chronic hepatitis B virus (HBV) infection is strongly associated with increased risk of liver cancer and cirrhosis. While existing treatments effectively inhibit the HBV life cycle, viral rebound frequently occurs following treatment interruption. Consequently, functional cure rates of chronic HBV infection remain low and there is increased interest in a novel treatment modality, capsid assembly modulators (CAMs). Here, we develop a multiscale mathematical model of CAM treatment in chronic HBV infection. By fitting the model to participant data from a phase I trial of the first-generation CAM vebicorvir, we estimate the drug’s dose-dependent effectiveness and identify the physiological mechanisms that drive the observed biphasic decline in HBV DNA and RNA, and mechanistic differences between HBeAg-positive and negative infection. Finally, we demonstrate analytically and numerically that the relative change of HBV RNA more accurately reflects the antiviral effectiveness of a CAM than the relative change in HBV DNA.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Antiviral Agents - pharmacology
/ Antiviral Agents - therapeutic use
/ DNA
/ HBV
/ Hepatitis B virus - drug effects
/ Hepatitis B virus - genetics
/ Hepatitis B virus - physiology
/ Hepatitis B, Chronic - drug therapy
/ Hepatitis B, Chronic - virology
/ Humans
/ Medicine and Health Sciences
/ Research and analysis methods
/ RNA
