Dynamics of an age‐structured multiscale hepatitis C virus model with two infection modes and antibody immune response

Abstract

The interference of direct‐acting antiviral agents (DAAs) within various steps of the life cycle of hepatitis C virus (HCV) results in a high cure rate for chronic HCV infection. To accurately quantify the effect of DAAs on treatment and to achieve an optimal drug combination for treatment, we formulate an age‐structured multiscale HCV model. This model incorporates intracellular virus RNA replication process corresponding to the mechanism of drug action, two modes of extracellular virus transmission (virus‐to‐cell infection and cell‐to‐cell infection), and antibody immune response. We prove that the threshold dynamics of the pre‐treatment model is completely determined by the basic reproduction number and the antibody immune reproduction number . Under reasonable assumptions, we obtain long‐term and short‐term approximations for post‐treatment viral loads and identify which approximation performs better under various scenarios. Numerical simulations show that the infection mode of cells mainly affects the reduction of viral load in the third stage, while the antibody immune response is mainly manifested in the clearance of viral particles in the first stage of viral load decrease. With effective treatments, blocking cell‐to‐cell infection and enhancing the antibody immune response can effectively reduce the viral load in a short time period achieving the eradication of infection. Our findings suggest that the HCV infection is highly dynamic post‐DAAs treatment, and early monitoring of viral load decline contributes to the implementation of subsequent treatment regimens.