Statistical Methods for Adherence and HIV Outcomes

说明(申请人提供)：尽管坚持服用抗逆转录病毒药物越来越被认为是成功治疗艾滋病毒的关键，但依从性的衡量和统计方法的发展落后于有效艾滋病毒治疗方法的发展。研究表明，坚持服用抗逆转录病毒药物是抑制病毒复制和增加CD4计数的核心，但确切的依从性-反应曲线以及坚持与艾滋病毒病毒学结果之间的关系还没有得到充分的探索。目前可用的遵守措施存在几个主要问题。首先，每种测量技术都存在显著的测量误差或偏差。其次，大多数措施只衡量服用处方药的百分比，而忽略了依从性行为的其他方面，如剂量间隔，这对于半衰期较短的药物，如艾滋病毒蛋白酶抑制剂，尤其重要。目前使用的单一遵守措施没有将遵守行为的不同方面整合在一起。第三，需要一种切实可行的、适用于患者护理环境的遵守措施。易于应用和低成本使自我报告最有吸引力的临床使用，但目前的调查方法无法收集信息的高度敏感性的不依从性。到目前为止，艾滋病毒药物依从性和病毒学结果之间的关系主要是使用带有依从性措施的横断面分析来表征的，这些依从性措施容易出错，并且只部分描述了依从性行为。利用收集了丰富的用药依从性和病毒学结果数据的两项纵向艾滋病毒研究的可用数据，我们建议开发收集和分析依从性数据的改进方法，并对依从性和病毒学结果之间的关系进行建模。这项研究将：1)创建能够全面和准确地描述用药依从性行为的多方面特征的测量方法；2)改进在临床护理背景下获得自我报告依从性信息的调查方法；以及3)使用重复测量分析，调查用药依从性与RNA病毒载量和耐药性的艾滋病毒病毒学结果之间的潜在纵向关系。

DESCRIPTION (provided by applicant): Although adherence to antiretroviral medications is increasingly recognized as critical to successful HIV treatment, the development of measurement and statistical methods for adherence lags behind the advancement in development of effective HIV therapies. Studies have shown that adherence to antiretroviral medications is central to suppression of viral replication and to increases in CD4 count, but the exact compliance-response curve and the relationship between adherence and HIV virologic outcomes over time have been inadequately explored. Currently available adherence measures have several major problems. First, there are significant measurement errors or bias associated with each of the measurement techniques. Secondly, most of the measures only measure the percent of prescribed medication taken, ignoring the other aspects of adherence behavior such as dose-interval, which is particularly important for medications with a short half-life such as HIV protease inhibitors. No single adherence measure currently in use integrates the different aspects of adherence behavior. Third, a practical adherence measure feasible for patient care settings is needed. Ease of application and low cost make self-report most appealing for clinical use, but current survey methods fail to gather information with high sensitivity for non-adherence. To date, the relationship between HIV medication adherence and virologic outcomes has been characterized principally using cross sectional analyses with adherence measures that are error-prone and that only partially describe adherence behavior. Using available data from two longitudinal HIV studies that collected rich medication adherence and virologic outcome data, we propose to develop improved methods of collecting and analyzing adherence data, and modeling the relationship between adherence and virologic outcomes. The study will: 1) create measures that can fully and accurately describe the multifaceted character of medication adherence behavior; 2) improve survey methods for obtaining self-report adherence information in the context of clinical care; and 3) using repeated measures analyses, investigate the underlying longitudinal relationship between medication adherence and HIV virologic outcomes of RNA viral load and drug resistance.