Modelling hepatitis C therapy—predicting effects of treatment

Abstract

After patients receive therapy for HCV infection, HCV RNA declines in a biphasic manner, the first phase reflects viral clearance, the second phase the loss of infected cells The use of mathematical modelling reveals that high viral production enables the daily production of all single or double mutant variants resulting in drug resistance for therapies with low genetic barriers Modelling HCV RNA kinetics has enabled researchers to estimate the effectiveness of therapy and optimal treatment duration to achieve a sustained virologic response (SVR) Multiscale models that include intracellular viral replication and extracellular spread indicate that NS5A and protease inhibitors can inhibit both viral replication and viral assembly or release Interferon-free combination therapies are available, have little resistance and can generate a SVR after treatment times as short as 6 weeks HCV RNA has been detected after treatment with some direct-acting antiviral combinations in patients who develop a SVR, but viral kinetic theory cannot currently explain this phenomenon