Mathematical and Experimental Models for HIV Dynamics

HIV 动力学的数学和实验模型

• 批准号: 7222791
• 负责人: SARAH E HOLTE
• 金额: $ 32.81万
• 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 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7222791
• 关键词: Mathematical; Experimental; Models; HIV; Dynamics

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，利用实验和临床数据来回答有关影响 HIV 感染动态的因素的问题。拟议的研究包括定量科学家和生物科学家之间的跨学科互动，并将指导数学模型的开发和分析。 相反，模型结果将指导进一步的实验和数据收集。 我们的研究基于常微分方程组和偏微分方程组，需要复杂的数学和统计分析。实验室和临床数据模型的开发固有地需要健全的统计方法。 非线性随机效应统计模型的严格计算和随机方法将应用于来自个体总体群体的各种数据。 目前，由于现有方法的计算成本极高，标准技术仅能部分满足需要。为了克服这一困难，将开发一种新的“集成数据”方法，用于非线性随机效应模型中的参数估计和推理。 具体的实验和临床研究将包括调查实验室实验中不同HIV病毒株之间竞争的影响以及临床数据分析，从而揭示HIV感染细胞群非线性衰变特征的本质。体外研究将基于数学模型进行设计，以评估靶细胞群大小对两种HIV病毒株动态的影响。实验室实验将在数学模型的指导下进行，并基于最近开发的培养系统进行，该系统可以控制受感染细胞的死亡率，以便可以在更类似于体内条件的环境中进行实验。体内临床分析将描述 HAART 后 HIV-1 感染细胞群的衰变行为。之前基于线性模型的预测，即从感染个体中根除病毒所需的时间，尚未在临床观察中实现。 此外，未来对艾滋病毒感染者的治疗和管理在很大程度上依赖于对受感染细胞群衰变特征的准确了解。 因此，迫切需要更准确地描述受感染细胞群的衰变特征。

项目成果

HIV-1 RNA may decline more slowly in semen than in blood following initiation of efavirenz-based antiretroviral therapy.

• DOI: 10.1371/journal.pone.0043086
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Graham SM;Holte SE;Dragavon JA;Ramko KM;Mandaliya KN;McClelland RS;Peshu NM;Sanders EJ;Krieger JN;Coombs RW
• 通讯作者: Coombs RW

IL28B genotype effects during early treatment with peginterferon and ribavirin in difficult-to-treat hepatitis C virus infection.

• DOI: 10.1093/infdis/jir264
• 发表时间: 2011-08
• 期刊: The Journal of infectious diseases
• 作者: John D. Scott;S. Holte;T. Urban;C. Burgess;E. Coppel;Chia Wang;L. Corey;J. Mchutchison;D. Goldstein