Myers Nicholas, Droz Dana, Rogers Bruce W, Tran Hien, Flores Kevin B, Chan Cliburn, Knechtle Stuart J, Jackson Annette M, Luo Xunrong, Chambers Eileen T, McCarthy Janice M
Center for Research in Scientific Computation, Department of Mathematics, North Carolina State University, Raleigh, NC 27695, USA.
Department of Surgery, Duke University, Durham, NC 27710, USA.
Viruses. 2024 Dec 31;17(1):50. doi: 10.3390/v17010050.
Kidney transplant recipients require a lifelong protocol of immunosuppressive therapy to prevent graft rejection. However, these same medications leave them susceptible to opportunistic infections. One pathogen of particular concern is human polyomavirus 1, also known as BK virus (BKPyV). This virus attacks kidney tubule epithelial cells and is a direct threat to the health of the graft. Current standard of care in BK virus-infected transplant recipients is reduction in immunosuppressant therapy, to allow the patient's immune system to control the virus. This requires a delicate balance; immune suppression must be strong enough to prevent rejection, yet weak enough to allow viral clearance. We seek to model viral and immune dynamics with the ultimate goal of applying optimal control methods to this problem. In this paper, we begin with a previously published model and make simplifying assumptions that reduce the number of parameters from 20 to 14. We calibrate our model using newly available patient data and a detailed sensitivity analysis. Numerical results for multiple patients are given to show that the newer model reflects observed dynamics well.
肾移植受者需要终身进行免疫抑制治疗方案，以防止移植排斥反应。然而，这些药物同样使他们易受机会性感染。一种特别值得关注的病原体是人类多瘤病毒1，也称为BK病毒（BKPyV）。这种病毒攻击肾小管上皮细胞，对移植器官的健康构成直接威胁。目前，BK病毒感染的移植受者的标准治疗方法是减少免疫抑制治疗，以使患者的免疫系统控制病毒。这需要微妙的平衡；免疫抑制必须足够强以防止排斥反应，但又要足够弱以允许病毒清除。我们试图对病毒和免疫动力学进行建模，最终目标是将最优控制方法应用于此问题。在本文中，我们从一个先前发表的模型开始，并做出简化假设，将参数数量从20个减少到14个。我们使用新获得的患者数据和详细的敏感性分析对模型进行校准。给出了多个患者的数值结果，以表明新模型能很好地反映观察到的动态。
