Modeling, Estimation and Control in HIV Dynamics

HIV 动力学的建模、估计和控制

• 批准号: 6640794
• 负责人: H. THOMAS BANKS
• 金额: $ 38.29万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6640794
• 关键词: AIDS; AIDS therapy; HIV infections; antiviral agents; clinical research; combination chemotherapy; host organism interaction; human data; human immunodeficiency virus; mathematical model; model design /development; statistics /biometry; virus infection mechanism

DESCRIPTION (provided by applicant): HIV-related illness is and will continue to be an important clinical and public health issue as well an international security, stability, and development issue. Although the advent of Highly Active Anti-Retroviral Therapy (HAART) has significantly reduced HIV-related morbidity and mortality, further advances in the treatment of HIV-infected individuals require a deeper understanding of the underlying mechanisms of the disease and how they are affected by these powerful treatments. For example, whether individuals may interrupt or discontinue treatment with control of infection is an important clinical question, insight into which may be gained by improved understanding of disease mechanisms. Indeed, as not all individuals experience the same level of treatment efficacy, it is imperative that variation in these mechanisms across individuals be elucidated. Mathematical models, in the form of systems of ordinary and delay differential equations, have been used to provide descriptions of the dynamics of the interactions of HIV and various compartments of the human immune system and thus formalize theorized mechanisms and have led to considerable recent insights. However, only simplified such models have been tested with clinical data; thus, there remain significant opportunities for mathematical modeling to contribute to enhanced understanding of HIV infection and associated immune response. The investigators will use advanced mathematical modeling and relevant statistical methods to develop new models for interactions among HIV, its target resources (T-cells, macrophages and/or dendritic cells), and the human immune system, with a particular emphasis on building models on the basis of clinical data wherever possible. They will test for and analyze nonlinear mathematical mechanisms in HIV infection dynamics and associated immune response using both ordinary and partial differential equations. In situations where data analysis suggests that nonlinearities in the models that describe the biology are relevant, they will perform numerical and/or qualitative analysis of the systems to identify stable behavior and bifurcations in the mathematical system, which in turn could provide insight into control of the biological system. Furthermore, they will develop and implement formal statistical and computational methods to estimate parameters in the models with emphasis on accounting for and exploring variability underlying mechanisms across different individuals. Finally. they will use the models and methods to address specific scientific questions, including analysis of differences in dynamic parameters based on a variety of host genotypes and development of optimal control methodologies designed to guide for structured treatment interruptions of HIV therapy.

描述（由申请人提供）：艾滋病毒相关疾病是，并将继续 是一个重要的临床和公共卫生问题，也是一个国际问题。 安全、稳定和发展问题。虽然高度的出现 积极的抗逆转录病毒治疗（HAART）显著减少了艾滋病毒相关的 发病率和死亡率，艾滋病毒感染者治疗的进一步进展， 个人需要更深入地了解的基本机制， 疾病以及它们如何受到这些强大治疗的影响。比如说， 个体是否可以中断或停止治疗， 感染是一个重要临床问题， 通过提高对疾病机制的理解。事实上，并不是所有的人 体验相同水平的治疗效果， 这些机制在个体之间的差异得到阐明。数学 模型，以常微分方程和延迟微分方程系统的形式， 已被用来提供的相互作用的动力学的描述 艾滋病毒和人类免疫系统的各个部分，从而正式 理论化的机制，并导致了相当多的最近的见解。然而，在这方面， 只有简化的这种模型已经用临床数据进行了测试;因此， 仍然是数学建模的重要机会， 加强对艾滋病毒感染和相关免疫反应的了解。 研究人员将使用先进的数学建模和相关的 统计方法，以开发新的模型之间的相互作用艾滋病毒，其 靶向资源（T细胞、巨噬细胞和/或树突细胞），以及人 免疫系统，特别强调建立模型的基础上， 尽可能提供临床数据。他们将测试和分析非线性 艾滋病毒感染动力学和相关免疫的数学机制 响应使用普通和偏微分方程。局势中 其中数据分析表明， 生物学是相关的，他们将进行数字和/或定性 分析系统，以确定稳定的行为和分叉， 数学系统，这反过来又可以提供洞察控制的 生物系统。 此外，他们还将制定和实施正式的统计和 计算方法来估计模型中的参数，重点是 解释和探索不同国家和地区的 个体终于来了他们将使用模型和方法来解决特定的 科学问题，包括分析动态参数的差异 基于多种宿主基因型和开发最优控制 旨在指导艾滋病毒治疗有组织中断的方法 疗法