Multi-Site Collaborative Study for Adherence Virologic and Clinical Outcomes

描述（由申请人提供）：尽管许多研究已经确定，坚持HIV药物治疗与病毒抑制、耐药性、疾病进展和死亡密切相关，但大多数数据收集的是过时的、部分抑制的方案，患者报告的依从性措施粗糙，样本量和统计能力有限。使用客观措施的调查只检查了传统的原始依从性百分比，尚未解决依从性行为的其他方面，如剂量定时。因此，关键问题仍未得到解答。例如，哪一种抗逆转录病毒药物（ARV）与最佳的依从性有关，依从性行为如何决定患者是否产生有限或多种耐药性，以及复杂的依从性行为（包括未被依从性百分比捕获的行为）如何影响病毒学和临床结果。此外，大多数使用传统依从性措施的研究仅将病毒抑制作为主要结果，而没有将其他临床重要结果（如CD4细胞丢失、疾病进展和死亡）作为主要结果。因为客观的依从性测量，如电子监测系统，是昂贵的，大多数大型研究都局限于自我报告或药房补充，这受到测量偏差，缺乏准确性和无法捕捉依从性行为的所有方面的限制，以客观地描述其对结果的影响。我们提出了一项多地点合作研究，将15项精心挑选的3003名个体的依从性与广泛覆盖的抗逆转录病毒药物和方案、人口统计学、社会心理和行为特征、病毒学和临床结果数据整合在一起。这个多站点合作研究将：(1)创建一个丰富而强大的数据源，由统计协调和分析中心协调，为广泛的研究人员解决任何单一数据集难以或不可能回答的重要问题；(2)建立并验证能够全面、客观、准确地表征多层面依从行为的依从性措施；(3)研究抗逆转录病毒药物依从性的模式和决定因素，并评估针对大量不同艾滋病毒人群的干预措施的有效性；(4)模拟抗逆转录病毒药物依从性、患者个性、用药和方案特征等因素随时间变化的病毒学结果、临床事件、疾病进展和死亡。

DESCRIPTION (provided by applicant): Although many studies have established that adherence to HIV medication is closely associated with viral suppression, drug resistance, disease progression and death, most data were collected on obsolete, partially suppressive regimens with coarse patient-reported adherence measures, limited sample size and statistical power. Investigations using objective measures have examined only traditional raw percent adherence and have not yet addressed other aspects of adherence behavior such as dose timing. As such, critical questions remain unanswered. For example, which single antiretroviral medication (ARV) is associated with the best adherence, how adherence behavior determines whether patients develop either limited or multi-drug resistance, and how complex adherence behavior, including that not captured by percent adherence, influences virologic and clinical outcomes. In addition, most studies that utilized traditional adherence measures only examined viral suppression as the primary outcome, but not other clinically important outcomes such as CD4 cell loss, disease progression and death. Because objective adherence measures, such as electronic monitoring systems, are expensive, most large studies have been limited to self-report or pharmacy refill, which are limited by measurement bias, lack of precision and inability to capture all aspects of adherence behavior in order to objectively describe their impact on outcomes. We propose a multi-site collaborative study that integrates adherence with wide coverage of ARVs and regimens, demographics, psychosocial and behavioral characteristics, and virologic and clinical outcomes data from 3,003 individuals across 15 carefully selected studies. This multi-site collaboration study will: (1) create a rich and powerful data source, coordinated by a Statistical Coordination and Analysis Center, for a broad range of investigators to address important questions that are difficult or impossible to answer with any single data set; (2) create and validate adherence measures that can characterize multi- faceted adherence behavior fully, objectively and accurately; (3) study patterns and determinants of adherence to ARVs, as well as evaluate the effectiveness of interventions with large, diverse HIV population; and (4) model virologic outcomes, clinical events, disease progression and death as functions of adherence to ARVs, patient individuality, medication and regimen characteristics and other factors over time.