Resonance of Periodic Combination Antiviral Therapy and Intracellular Delays in Virus Model
Resonance of Periodic Combination Antiviral Therapy and Intracellular Delays in Virus Model
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DOI：
10.1007/s11538-020-00704-3
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发表时间：
2020-02
影响因子：
3.5
通讯作者：
C. Browne;Xuejun Pan;Hongying Shu;Xiang-Sheng Wang
中科院分区：
文献类型：
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作者：
C. Browne;Xuejun Pan;Hongying Shu;Xiang-Sheng Wang
人们对病毒感染和抗病毒药物动力学的详细模型非常感兴趣，以便优化针对病毒如HIV的治疗。在本文中，我们研究了一般的细胞内分布延迟和周期性联合抗病毒治疗下的病毒内动力学。基本再生数被建立为决定消光与持续的全局阈值，光谱方法被用于分析和数值计算。我们推导出病毒的临界成熟延迟和各种细胞内延迟下正弦变化的药物效力之间的最佳相位差。此外，数值模拟进行利用现实的药代动力学和伽马分布的病毒生产延迟艾滋病毒。我们的研究结果表明，关键病毒复制周期步骤的相对时间和涉及不同药物的周期性抗病毒治疗方案都可以相互作用，严重影响整体病毒动力学。
There is a substantial interest in detailed models of viral infection and antiviral drug kinetics in order to optimize the treatment against viruses such as HIV. In this paper, we study within-viral dynamics under general intracellular distributed delays and periodic combination antiviral therapy. The basic reproduction numberis established as a global threshold determining extinction versus persistence, and spectral methods are utilized for analytical and numerical computations of. We derive the critical maturation delay for virus and optimal phase difference between sinusoidally varying drug efficacies under various intracellular delays. Furthermore, numerical simulations are conducted utilizing realistic pharmacokinetics and gamma-distributed viral production delays for HIV. Our results demonstrate that the relative timing of the key viral replication cycle steps and periodic antiviral treatment schedule involving distinct drugs all can interact to critically affect the overall viral dynamics.