AIDS Clinical Trail Modeling and Stimulatinos

项目描述（申请人提供）：本项目旨在结合HIV/AIDS研究中的数学建模、统计方法、计算机模拟、药代动力学/药效学和临床/生物科学等新技术，开发用于艾滋病临床试验的模拟系统。我们期望试验模拟系统能够帮助设计复杂的艾滋病临床试验，优化复杂的艾滋病治疗策略，研究HIV感染的生物学机制和艾滋病的发病机制，从而为临床试验提供新的生物学假设。首先，将为艾滋病临床试验模拟开发数学/统计模型。这些模型包括纳入药代动力学和依从性信息的药物暴露模型、药物敏感性（耐药性）模型、药物疗效和抗病毒反应模型。将开发用于估计模型参数和从模拟数据进行推断的统计方法。在建立模型的基础上，将开发计算机仿真系统。提出了几个仿真项目来测试和验证仿真系统。我们期望开发的艾滋病临床试验模拟系统可以被艾滋病临床医生用于设计新的艾滋病临床试验和探索新的治疗策略，而不会危及人类受试者。艾滋病医生和患者也可以使用模拟系统来预测和监测抗逆转录病毒治疗的结果。开发的系统将成为艾滋病临床医生为其患者开发个性化治疗的有用工具。

DESCRIPTION (provided by applicant): This project aims to combine new technologies in mathematical modeling, statistical methods, computer simulations, pharmacokinetics/pharmacodynamics, and clinical/biological sciences in HIV/AIDS research to develop simulation systems for AIDS clinical trials. We expect that the trial simulation systems can help with design of complicated AIDS clinical trials, to optimize sophisticated AIDS treatment strategies, and to study biological mechanisms of HIV infection and AIDS pathogenesis so that new biological hypotheses can be generated for clinical tests. First, mathematical/statistical models will be developed for AIDS clinical trial simulations. These models include drug exposure models for incorporating pharmacokinetics and adherence information, drug sensitivity (resistance) models, drug efficacy and antiviral response models. Statistical methods for estimating model parameters and for making inferences from simulation data will be developed. Based on the established models, computer simulation systems will be developed. Several simulation projects are proposed to test and validate the simulation systems. We expect that the developed AIDS clinical trial simulation systems can be used by AIDS clinicians to design new AIDS clinical trials and to explore new treatment strategies without risking human subjects. AIDS physicians and patients may also use the simulation systems to predict and monitor the outcomes of an antiretroviral treatment. The developed systems will be a useful tool for AIDS clinicians to develop individualized treatments for their patients.