Viral Rebound After Antiviral Treatment: A Mathematical Modeling Study of the Role of Antiviral Mechanism of Action.

The development of antiviral treatments for SARS-CoV-2 was an important turning point for the pandemic. Availability of safe and effective antivirals has allowed people to return back to normal life. While SARS-CoV-2 antivirals are highly effective at preventing severe disease, there have been concerning reports of viral rebound in some patients after cessation of antiviral treatment. In this study, we use a mathematical model of viral infection to study the potential of different antivirals to prevent viral rebound. We find that antivirals that block production are most likely to result in viral rebound if the treatment time course is not sufficiently long. Since these antivirals do not prevent infection of cells, cells continue to be infected during treatment. When treatment is stopped, the infected cells will begin producing virus at the usual rate. Antivirals that prevent infection of cells are less likely to result in viral rebound since cells are not being infected during treatment. This study highlights the role of antiviral mechanism of action in increasing or reducing the probability of viral rebound.