Analytical Methods/HIV Treatment and Co-factor Effects

描述（由申请人提供）：本提案的主要目的是进一步发展分析艾滋病毒感染者的观察性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开放性实质性问题。所提出的方法是基于(i)估计新的类型的因果模型，包括结构嵌套模型、边际结构模型（msm）、直接效应结构嵌套模型、连续时间结构嵌套模型和最优状态结构模型（SNMs）。许多新方法从根本上说是“流行病学的”，因为它们需要时间相关的混杂因素的数据，即影响结果的风险因素，这些因素也可以预测所研究药物或辅助因素的后续治疗。

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.