Nonparametric Modeling of Long-term HIV/Cell Dynamics

描述（由申请人提供）：本提案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。第一个具体目标是为纵向HIV/ t细胞动态数据开发灵活有效的非参数回归模型和推理工具。这些包括：（1a）开发灵活有效的纵向数据非参数回归方法。这些将包括研究和扩展局部核回归方法和基于基的回归样条方法的纵向数据分析；（1b）研究已开发的非参数估计方法的渐近和有限样本性质。比较和评估不同的方法，并提出最佳的实际应用方法；（1c）发展具有纵向数据的非参数回归模型的统计推断方法；(i)开发计算机程序或软件，以实施建议的方法。第二个目标是利用艾滋病临床试验组（ACTG）开发的艾滋病临床试验数据，应用已开发的方法来研究hiv - tt细胞的长期动力学。这些包括：（2a）利用纵向数据的灵活非参数回归方法表征接受HAART治疗的HIV- i感染患者的长期HIV- tt细胞动力学，并研究长期抗逆转录病毒药物暴露环境中HIV- T细胞动力学与长期HIV动力学之间的关系；（2b）确定哪些药理学、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）探索如何利用HIV/ t细胞的长期动态模式来评估抗逆转录病毒疗法的长期有效性。通过对HIV和T细胞的长期动力学建模，我们可以对慢性HIV感染的发病机制有更深入的了解。我们期望该项目的结果可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.