Department of Pharmaceutics, School of Pharmacy, University College London, London, UK.
Infection, Immunity and Inflammation Research and Teaching Department, Great Ormond Street Institute of Child Health, University College London, London, UK.
CPT Pharmacometrics Syst Pharmacol. 2023 Oct;12(10):1450-1460. doi: 10.1002/psp4.13022. Epub 2023 Aug 21.
Mathematical models of viral dynamics have been reported to describe adequately the dynamic changes of severe acute respiratory syndrome-coronavirus 2 viral load within an individual host. In this study, eight published viral dynamic models were assessed, and model selection was performed. Viral load data were collected from a community surveillance study, including 2155 measurements from 162 patients (124 household and 38 non-household contacts). An extended version of the target-cell limited model that includes an eclipse phase and an immune response component that enhances viral clearance described best the data. In general, the parameter estimates showed good precision (relative standard error <10), apart from the death rate of infected cells. The parameter estimates were used to simulate the outcomes of a clinical trial of the antiviral tixagevimab-cilgavimab, a monoclonal antibody combination which blocks infection of the target cells by neutralizing the virus. The simulated outcome of the effectiveness of the antiviral therapy in controlling viral replication was in a good agreement with the clinical trial data. Early treatment with high antiviral efficacy is important for desired therapeutic outcome.
已报道的病毒动力学数学模型能够充分描述个体宿主中严重急性呼吸综合征冠状病毒 2 病毒载量的动态变化。本研究评估了 8 个已发表的病毒动力学模型，并进行了模型选择。病毒载量数据来自社区监测研究，包括 162 名患者（124 名家庭接触者和 38 名非家庭接触者）的 2155 次测量。扩展的靶细胞有限模型，包括潜伏期和增强病毒清除的免疫反应部分，能够最好地描述数据。总的来说，除了感染细胞的死亡率外，参数估计值具有很好的精度（相对标准误差<10%）。这些参数估计值用于模拟抗病毒药物 tixagevimab-cilgavimab 的临床试验结果，该药物是一种单克隆抗体组合，通过中和病毒来阻断靶细胞的感染。抗病毒治疗控制病毒复制的有效性的模拟结果与临床试验数据非常吻合。早期使用高抗病毒疗效的治疗对于获得理想的治疗效果很重要。
