Within-Host Viral Dynamics in a Multi-compartmental Environment.

Abstract

The discrepancy in the turnover of cells and virus in different organs or viral reservoirs necessitates the investigation of multiple compartments within a host. Establishing a multi-compartmental structure that describes the complexity of various organs, where viral infection comprehensively proceeds, provides a modeling framework for exploring the effect of spatial heterogeneity on viral dynamics. To successfully suppress within-host viral replication, it is imperative to determine drug administration during therapy, particularly for a combination of antiretroviral drugs. The proposed model provides quantitative insights into pharmacokinetics and the resulting virus population, which substantially relates to environmental heterogeneity. The main results are the following: (1) A model incorporating drug treatment admits threshold dynamics, driving to either viral extinction or uniform persistence, regardless of non-trivial initial infection, in the entire system. (2) Viral infection may be underestimated if a well-mixed (single-compartmental) model is used. (3) Optimal drug administration depends not only on the drug distribution over various compartments but also on the timing, described by phase shifts, of the administration of different drugs in a combined therapy.