Nonparametric Modeling of Long-term HIV/Cell Dynamics

描述(由申请人提供)：这项建议旨在开发灵活的非参数回归方法和统计推断工具，用于模拟接受高效抗逆转录病毒疗法(HAART)治疗的HIV-1感染患者的长期HIV和T淋巴细胞动力学。第一个具体目标是开发灵活有效的非参数回归模型和推理工具，用于纵向HIV/T细胞动态数据。这些措施包括：(1)开发灵活有效的纵向数据非参数回归方法。这些将包括研究和推广用于纵向数据分析的局部核回归方法和基于基回归样条法；(1b)研究发展的非参数估计方法的渐近和有限样本性质。比较和评价不同的方法，并提出最适合实际应用的方法；(1)开发具有纵向数据的非参数回归模型的统计推断方法；(ID)开发计算机程序或软件来实施所提出的方法。第二个目标是利用艾滋病临床试验小组(ACTG)开发的艾滋病临床试验的数据，应用开发的方法来研究HIVTT细胞的长期动力学。这些研究包括：(2a)使用灵活的非参数回归方法对HAART治疗的HIV-I感染患者的长期HIVTT细胞动力学进行表征，并研究长期抗逆转录病毒药物暴露环境下HIV长期动态与T淋巴细胞动力学的关系；(2b)确定哪些药理、临床和宿主特异性因素影响HIV和T淋巴细胞的长期动态；(2c)研究临床终点与HIV和T淋巴细胞长期动态模式的关系；(2D)探讨如何使用长期艾滋病毒/T细胞动态模式来评估抗逆转录病毒治疗的长期有效性。通过建立HIV和T细胞的长期动态模型，可以对HIV慢性感染的发病机制有更深入的认识。我们期待该项目的结果可以用于评估抗逆转录病毒疗法的长期有效性，并为艾滋病毒感染患者的长期护理和治疗管理提供信息。

DESCRIPTION (provided by applicant): This proposal intends to develop flexible nonparametric regression methods and statistical inference tools for modeling long-term HIV and T lymphocyte dynamics in HIV-1 -infected patients treated with highly active antiretroviral therapies (HAART). The first specific aim is to develop flexible and efficient nonparametric regression models and inference tools for longitudinal HIV/T-cell dynamic data. These include: (1a) to develop flexible and efficient nonparametric regression methods for longitudinal data. These will include the investigation and extension of local kernel regression methods and basis-based regression splines methods for longitudinal data analysis; (1b) to study the asymptotic and finite-sample properties of the developed nonparametric estimation methods. To compare and evaluate different methods, and to propose the best one for practical use; (1c) to develop statistical inference methods for nonparametric regression models with longitudinal data; (Id) to develop computer programs or software to implement the proposed methodologies. The second aim is to apply the developed methods to study long-term HIVTT-cell dynamics using the data from AIDS clinical trials developed by the AIDS Clinical Trials Group (ACTG). These include: (2a) to characterize long-term HIVTT-cell dynamics in HIV-I-infected patients treated with HAART using flexible nonparametric regression methods for longitudinal data, and to study the relationship between long-term HIV dynamics and T lymphocyte kinetics in the environment of long-term antiretroviral drug exposure; (2b) to identify what pharmacological, clinical and host-specific factors affect the long-term dynamics of HIV and T lymphocytes; (2c) to study the relationships between clinical endpoints and the long-term dynamic patterns of HIV and T lymphocytes; (2d) to explore how the long-term HIV/T-cell dynamic patterns can be used to assess the long-term effectiveness of antiretroviral therapies. We may gain more and deep understanding of pathogenesis of chronic HIV infection via modeling the long-term dynamics of HIV and T cells. We expect that the results from this project can be used to assess the long-term effectiveness of antiretroviral therapies and provide information for long-term care and treatment management for HIV-I-infected patients.