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，但大多数数据都是在过时的、部分抑制性方案上收集的，患者报告的依从性指标粗糙，样本量和统计功效有限。使用客观指标的研究仅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，如给药时间。因此，关键问题仍然没有答案。例如，哪种抗逆转录病毒药物（ARV）与最佳依从性相关，依从性行为如何决定患者是否产生有限或多药耐药性，以及复杂的依从性行为（包括未通过依从性百分比捕获的依从性行为）如何影响病毒学和临床结果。此外，大多数使用传统依从性指标的研究仅将病毒抑制作为主要结局进行检查，而没有检查其他临床重要结局，如CD 4细胞丢失、疾病进展和死亡。由于客观的依从性措施，如电子监测系统，是昂贵的，大多数大型研究已被限制为自我报告或药房补充，这是有限的测量偏差，缺乏精度和无法捕捉的所有方面的依从性行为，以客观地描述其对结果的影响。我们提出了一项多中心合作研究，将依从性与广泛覆盖的抗逆转录病毒药物和治疗方案，人口统计学，心理社会和行为特征以及来自15项精心选择的研究中的3，003名个体的病毒学和临床结局数据相结合。这项多中心协作研究将：（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，供广泛的研究人员解决难以或不可能用任何单一数据集回答的重要问题;（2）创建和验证可以全面、客观和准确地表征多方面依从性行为的依从性测量;（3）研究抗逆转录病毒药物依从性的模式和决定因素，以及评估对大量不同艾滋病毒感染者进行干预的有效性;（4）建立病毒学结果、临床事件、疾病进展和死亡模型，作为抗逆转录病毒药物依从性、患者个体、药物和方案特征以及其他因素随时间变化的函数。

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.