Analytical Methods/HIV Treatment and Co-factor Effects

说明(申请人提供)：这项建议的主要目的是进一步开发分析艾滋病毒感染者的观察数据库和随机试验的新方法，并将这些方法应用于随机和观察性研究中获得的数据，试图帮助回答有关艾滋病毒相关疾病的治疗和病程的重要的公开实质性问题。所提出的方法要么基于(I)估计新的因果模型，包括结构嵌套模型、边缘结构模型(MSM)、直接影响结构嵌套模型、连续时间结构嵌套模型和最优制度结构模型(SNM)。许多新方法基本上是“流行病学”的，因为它们需要依赖于时间的混杂因素的数据，也就是结果的风险因素，也就是预测随后使用研究中的药物或辅因子进行治疗的风险因素。 特别是，我们计划使用最佳方案SNM来帮助确定开始HAART治疗的最佳时间，并根据受试者的CD4计数、HIV RNA、临床病史以及可能的基因或表型耐药性测试结果来改变HAART方案。具体地说，我们计划与合作者一起重新分析来自多中心艾滋病队列研究、女性机构间艾滋病毒研究、瑞士艾滋病毒队列研究、蛋白酶抑制剂ERA后果研究(Scope)、法国医院艾滋病毒数据库(FHDH)研究、儿科晚期结局协议(PACTG 219)和ALLRT研究的数据。

DESCRIPTION (provided by applicant): The principal aim of this proposal is to further development of new methods for analyzing observational data bases and randomized trials of HIV-infected persons and the application of these methods to data obtained in randomized and observational studies in an attempt to help answer important open substantive questions concerning the treatment and course of HIV-related disease. The proposed approaches are based either on (i) the estimation of new classes of causal models which include structural nested models, marginal structural models (MSMs), direct effect structural nested models, continuous time structural nested models, and optimal regime structural models (SNMs). Many of the new methods are fundamentally "epidemiologic" in that they require data on time-dependent confounding factors, that is, risk factors for outcomes that also predict subsequent treatment with the drug or cofactor under study. In particular, we plan to use optimal regime SNMs to help determine the optimal times to start HAART therapy and to change HAART regimens as a function of a subject's CD4 count, HIV RNA, clinical history, and, where available, results of genotypic or phenotypic resistance testing. Specifically, we plan to reanalyze, with collaborators, data from the Multicenter AIDS Cohort Study, The Women's Interagency HIV Study, The Swiss HIV Cohort Study, The Study of The Consequences of Protease Inhibitor Era (SCOPE), the French Hospital Database on HIV (FHDH) study, the Pediatric Late Outcomes Protocol (PACTG 219) and the ALLRT study.