{"title":"由药物依从性驱动的随机 HIV 动态模型的不确定性量化。","authors":"Dingding Yan , Mengqi He , Sanyi Tang","doi":"10.1016/j.jtbi.2024.111895","DOIUrl":null,"url":null,"abstract":"<div><p>In HIV drug therapy, the high variability of CD<span><math><msup><mrow><mn>4</mn></mrow><mrow><mo>+</mo></mrow></msup></math></span> T cells and viral loads brings uncertainty to the determination of treatment options and the ultimate treatment efficacy, which may be the result of poor drug adherence. We develop a dynamical HIV model coupled with pharmacokinetics, driven by drug adherence as a random variable, and systematically study the uncertainty quantification, aiming to construct the relationship between drug adherence and therapeutic effect. Using adaptive generalized polynomial chaos, stochastic solutions are approximated as polynomials of input random parameters. Numerical simulations show that results obtained by this method are in good agreement, compared with results obtained through Monte Carlo sampling, which helps to verify the accuracy of approximation. Based on these expansions, we calculate the time-dependent probability density functions of this system theoretically and numerically. To verify the applicability of this model, we fit clinical data of four HIV patients, and the goodness of fit results demonstrate that the proposed random model depicts the dynamics of HIV well. Sensitivity analyses based on the Sobol index indicate that the randomness of drug effect has the greatest impact on both CD<span><math><msup><mrow><mn>4</mn></mrow><mrow><mo>+</mo></mrow></msup></math></span> T cells and viral loads, compared to random initial values, which further highlights the significance of drug adherence. The proposed models and qualitative analysis results, along with monitoring CD<span><math><msup><mrow><mn>4</mn></mrow><mrow><mo>+</mo></mrow></msup></math></span> T cells counts and viral loads, evaluate the influence of drug adherence on HIV treatment, which helps to better interpret clinical data with fluctuations and makes several contributions to the design of individual-based optimal antiretroviral strategies.</p></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"592 ","pages":"Article 111895"},"PeriodicalIF":1.9000,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Uncertainty quantification for the random HIV dynamical model driven by drug adherence\",\"authors\":\"Dingding Yan , Mengqi He , Sanyi Tang\",\"doi\":\"10.1016/j.jtbi.2024.111895\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>In HIV drug therapy, the high variability of CD<span><math><msup><mrow><mn>4</mn></mrow><mrow><mo>+</mo></mrow></msup></math></span> T cells and viral loads brings uncertainty to the determination of treatment options and the ultimate treatment efficacy, which may be the result of poor drug adherence. We develop a dynamical HIV model coupled with pharmacokinetics, driven by drug adherence as a random variable, and systematically study the uncertainty quantification, aiming to construct the relationship between drug adherence and therapeutic effect. Using adaptive generalized polynomial chaos, stochastic solutions are approximated as polynomials of input random parameters. Numerical simulations show that results obtained by this method are in good agreement, compared with results obtained through Monte Carlo sampling, which helps to verify the accuracy of approximation. Based on these expansions, we calculate the time-dependent probability density functions of this system theoretically and numerically. To verify the applicability of this model, we fit clinical data of four HIV patients, and the goodness of fit results demonstrate that the proposed random model depicts the dynamics of HIV well. Sensitivity analyses based on the Sobol index indicate that the randomness of drug effect has the greatest impact on both CD<span><math><msup><mrow><mn>4</mn></mrow><mrow><mo>+</mo></mrow></msup></math></span> T cells and viral loads, compared to random initial values, which further highlights the significance of drug adherence. The proposed models and qualitative analysis results, along with monitoring CD<span><math><msup><mrow><mn>4</mn></mrow><mrow><mo>+</mo></mrow></msup></math></span> T cells counts and viral loads, evaluate the influence of drug adherence on HIV treatment, which helps to better interpret clinical data with fluctuations and makes several contributions to the design of individual-based optimal antiretroviral strategies.</p></div>\",\"PeriodicalId\":54763,\"journal\":{\"name\":\"Journal of Theoretical Biology\",\"volume\":\"592 \",\"pages\":\"Article 111895\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2024-07-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Theoretical Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0022519324001796\",\"RegionNum\":4,\"RegionCategory\":\"数学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Theoretical Biology","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0022519324001796","RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
在艾滋病药物治疗中,CD4+ T 细胞和病毒载量的高变异性给治疗方案的确定和最终疗效带来了不确定性,这可能是药物依从性差的结果。我们建立了一个由药物依从性作为随机变量驱动的、与药物动力学耦合的 HIV 动态模型,并对不确定性量化进行了系统研究,旨在构建药物依从性与治疗效果之间的关系。利用自适应广义多项式混沌,将随机解近似为输入随机参数的多项式。数值模拟结果表明,与蒙特卡洛抽样得出的结果相比,该方法得出的结果非常一致,这有助于验证近似的准确性。基于这些展开,我们从理论和数值上计算了该系统随时间变化的概率密度函数。为了验证该模型的适用性,我们拟合了四名艾滋病患者的临床数据,拟合结果表明所提出的随机模型很好地描述了艾滋病的动态变化。基于 Sobol 指数的敏感性分析表明,与随机初始值相比,药物作用的随机性对 CD4+ T 细胞和病毒载量的影响最大,这进一步凸显了坚持服药的重要性。所提出的模型和定性分析结果,以及对 CD4+ T 细胞计数和病毒载量的监测,评估了药物依从性对艾滋病治疗的影响,有助于更好地解释有波动的临床数据,并为设计基于个体的最佳抗逆转录病毒策略做出了一些贡献。
Uncertainty quantification for the random HIV dynamical model driven by drug adherence
In HIV drug therapy, the high variability of CD T cells and viral loads brings uncertainty to the determination of treatment options and the ultimate treatment efficacy, which may be the result of poor drug adherence. We develop a dynamical HIV model coupled with pharmacokinetics, driven by drug adherence as a random variable, and systematically study the uncertainty quantification, aiming to construct the relationship between drug adherence and therapeutic effect. Using adaptive generalized polynomial chaos, stochastic solutions are approximated as polynomials of input random parameters. Numerical simulations show that results obtained by this method are in good agreement, compared with results obtained through Monte Carlo sampling, which helps to verify the accuracy of approximation. Based on these expansions, we calculate the time-dependent probability density functions of this system theoretically and numerically. To verify the applicability of this model, we fit clinical data of four HIV patients, and the goodness of fit results demonstrate that the proposed random model depicts the dynamics of HIV well. Sensitivity analyses based on the Sobol index indicate that the randomness of drug effect has the greatest impact on both CD T cells and viral loads, compared to random initial values, which further highlights the significance of drug adherence. The proposed models and qualitative analysis results, along with monitoring CD T cells counts and viral loads, evaluate the influence of drug adherence on HIV treatment, which helps to better interpret clinical data with fluctuations and makes several contributions to the design of individual-based optimal antiretroviral strategies.
期刊介绍:
The Journal of Theoretical Biology is the leading forum for theoretical perspectives that give insight into biological processes. It covers a very wide range of topics and is of interest to biologists in many areas of research, including:
• Brain and Neuroscience
• Cancer Growth and Treatment
• Cell Biology
• Developmental Biology
• Ecology
• Evolution
• Immunology,
• Infectious and non-infectious Diseases,
• Mathematical, Computational, Biophysical and Statistical Modeling
• Microbiology, Molecular Biology, and Biochemistry
• Networks and Complex Systems
• Physiology
• Pharmacodynamics
• Animal Behavior and Game Theory
Acceptable papers are those that bear significant importance on the biology per se being presented, and not on the mathematical analysis. Papers that include some data or experimental material bearing on theory will be considered, including those that contain comparative study, statistical data analysis, mathematical proof, computer simulations, experiments, field observations, or even philosophical arguments, which are all methods to support or reject theoretical ideas. However, there should be a concerted effort to make papers intelligible to biologists in the chosen field.