TY - JOUR
T1 - Within-Host Viral Dynamics in a Multi-compartmental Environment
AU - Chen, Shyan Shiou
AU - Cheng, Chang Yuan
AU - Rong, Libin
N1 - Publisher Copyright:
© 2019, Society for Mathematical Biology.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
AB - 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.
KW - Heterogeneous environment
KW - Optimal drug administration
KW - Periodic drug treatment
KW - Viral invasion threshold
KW - Within-host virus
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U2 - 10.1007/s11538-019-00658-1
DO - 10.1007/s11538-019-00658-1
M3 - Article
C2 - 31432306
AN - SCOPUS:85071180271
SN - 0092-8240
VL - 81
SP - 4271
EP - 4308
JO - Bulletin of Mathematical Biology
JF - Bulletin of Mathematical Biology
IS - 10
ER -