Mathematical and Experimental Models for HIV Dynamics

HIV 动力学的数学和实验模型

• 批准号: 6874937
• 负责人: SARAH E HOLTE
• 金额: $ 34.6万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6874937
• 关键词: HIV infections; clinical research; human data; longitudinal human study; mathematical model; model design /development; statistics /biometry; virus infection mechanism

DESCRIPTION (provided by applicant): The research in this proposal focuses on using mathematical and statistical models to answer questions about factors that affect the dynamics of HIV infection using both experimental and clinical data. The proposed research consists of interdisciplinary interactions between quantitative and biological scientists and will guide the development and analysis of the mathematical models. Conversely, model outcomes will direct further experiments and data collection. Our investigations are based on systems of ordinary and partial differential equations and will require sophisticated mathematical and statistical analysis. The need for sound statistical methods is inherent in the development of models for laboratory and clinical data. Rigorous computational and stochastic methods for nonlinear random effects statistical models will be applied to a variety of data from aggregate populations of individuals. At present, standard techniques are only partially adequate due to the extreme computational costs of existing methods. To overcome this difficulty, a new "integrated data" method for parameter estimation and inference in nonlinear random effects models will be developed. Specific experimental and clinical research will include investigating the effects of competition between various strains of HIV in laboratory experiments and analysis of clinical data that will reveal the nature of nonlinear decay characteristics of populations of HIV-infected cells. The in vitro study will be designed based on mathematical models to assess the effects of the target-cell population size on the dynamics of two strains of HIV Laboratory experiments will guide and be guided by mathematical models and be conducted based on a recently developed culture system that allows control over the infected cell death rate so that the experiments can be conducted in a setting more similar to the in vivo condition. The in vivo clinical analysis will characterize the decay behavior for populations of HIV-1 infected cells following HAART. Previous predictions---based on linear models---of the time needed for viral eradication from an infected individual have not been realized in clinical observations. Furthermore, future treatment and management of HIV infected individuals relies heavily on an accurate understanding of the decay characteristics of infected cell populations. Thus there is an urgent need to more accurately describe the decay profile of infected cell populations.

描述（由申请人提供）：本提案中的研究重点是使用数学和统计模型来回答有关使用实验和临床数据影响HIV感染动态的因素的问题。拟议的研究包括定量和生物科学家之间的跨学科相互作用，并将指导数学模型的发展和分析。 相反，模型结果将指导进一步的实验和数据收集。 我们的研究基于普通和部分微分方程的系统，将需要复杂的数学和统计分析。对实验室和临床数据模型的开发，对声音统计方法的需求是固有的。 非线性随机效应的严格计算和随机方法统计模型将应用于个人总体种群的各种数据。 目前，由于现有方法的极端计算成本，标准技术仅部分足够。为了克服这一困难，将开发一种新的“综合数据”方法，用于参数估计和推断非线性随机效应模型。 特定的实验和临床研究将包括研究HIV各种菌株在实验室实验中的竞争影响以及对临床数据的分析，这将揭示非线性衰变特征的性质。体外研究将基于数学模型设计，以评估目标细胞种群大小对两种HIV实验室实验菌株动力学的影响，并以数学模型为指导，并根据最近开发的培养系统进行指导，该培养系统可以控制受感染的细胞死亡率，从而可以在VIVO条件下进行更类似的情况进行实验。体内临床分析将表征HAART后HIV-1感染细胞种群的衰减行为。以前的预测 - 基于线性模型 - 在临床观察中尚未实现从感染者消除病毒所需的时间。 此外，对艾滋病毒感染者的未来治疗和管理在很大程度上依赖于对感染细胞群体的衰减特征的准确理解。 因此，迫切需要更准确地描述感染细胞群体的衰减曲线。