Analytic Methods for HIV Treatment and Co-Factor Effects

这项建议的主要目的是进一步发展分析观测数据的新方法。 艾滋病毒感染者的基础和随机试验以及这些方法对获得的数据的应用 在随机和观察性研究中，试图帮助回答重要的公开实质性问题 关于HLV相关疾病的治疗和病程。建议的方法基于以下两种情况 (I)估计新的因果模型类，其中包括结构嵌套模型、边际模型 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optimail制度结构模型(SNM)。许多新方法从根本上讲是“流行病学”的。 因为他们需要与时间相关的混杂因素的数据，也就是结果的风险因素 预测研究中的药物或辅因子的后续治疗。 特别是，我们计划进一步开发最优制度SNM和动态MSM，以帮助确定 开始HAART治疗和改变HAART方案的最佳时间作为受试者CD4的函数 计数，HIV RNA，临床病史，如果有的话，Genot^lc或表型耐药性测试的结果。 我们的方法将以指导分析和重新分析数据为目标，与合作者一起 来自HSPH的HIV致因共生。妇女机构间多人艾滋病队列研究 HIV研究，瑞士HIV队列研究，蛋白酶抑制剂Era的后果研究 (SCOPE)、儿科晚期结局方案(PACTG 219)和ALLRT研究。 相关性(请参阅说明)： 观察法被用来回答那些不可能或还没有被发现的紧迫的因果问题。 在随机试验中进行研究。特别是，我们正在开发最好的方法来确定 HIV感染者启动HAART治疗的最佳CD4和HIV RNA水平以及 一旦对最初的HAART方案产生耐药性，改变治疗的最佳时间。

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 HlV-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 optimail 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 further develop optimal regime SNMs and dynamic MSMs to help detemnine 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 genot^lc or phenotypic resistance testing. Our methods will be developed with the goal of directing analyzes and reanalyzes, with collaborators, of data from the HIV Causal Colioboration at HSPH . the Multicenler AIDS Cohort Study, The Women's Interagency HIV Study, The Swiss HIV Cohort Study, The Study of The Consequences of Protease Inhibitor Era (SCOPE), Pediatric Late Outcomes Protocol (PACTG 219) and the ALLRT study. RELEVANCE (See instructions): Observational methods are used to answer pressing causal questions that cannot be or have not yet been studied in randomized trials. In particular we are developing methods that are the best available to determine the optimal CD4 and HIV RNA levels at which to initiate HAAART therapy in HIV infected subjects and the optimal time to change therapy once resistance to a initial HAART regime has developed.