Statistical Methods for Adherence and HIV Outcomes

描述（由申请人提供）：尽管坚持抗逆转录病毒药物治疗越来越被认为是成功治疗艾滋病毒的关键，但坚持治疗的测量和统计方法的发展滞后于有效艾滋病毒治疗的发展。研究表明，坚持抗逆转录病毒药物对抑制病毒复制和增加CD4计数至关重要，但确切的依从性-反应曲线以及依从性与HIV病毒学结果之间的关系随着时间的推移尚未得到充分探索。目前可用的依从性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，大多数措施只测量处方药物的服用百分比，而忽略了依从性行为的其他方面，如剂量间隔，这对于半衰期短的药物（如HIV蛋白酶抑制剂）尤其重要。目前没有单一的依从性测量方法可以整合依从性行为的不同方面。第三，需要一种切实可行的依从性措施，适用于患者护理环境。易于应用和低成本使自我报告在临床应用中最具吸引力，但目前的调查方法未能收集到对不依从性具有高灵敏度的信息。迄今为止，HIV药物依从性和病毒学结果之间的关系主要是通过横断面分析来表征的，这些分析采用的依从性措施容易出错，而且只能部分描述依从性行为。利用来自两项HIV纵向研究的现有数据，收集了丰富的药物依从性和病毒学结果数据，我们建议开发改进的方法来收集和分析依从性数据，并建立依从性和病毒学结果之间的关系模型。本研究将：1)建立能够全面准确描述药物依从性行为的多方面特征的测量方法；2)改进临床护理中自我报告依从性信息的调查方法；3)通过重复测量分析，探讨药物依从性与HIV病毒学结果（RNA病毒载量和耐药性）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.