Global Immunological Response to Effective Antiretroviral Therapy (GiREAT:CD4)

描述（由申请人提供）：CD4细胞计数已被证明在开始有效的抗逆转录病毒治疗（ART）后最初急剧增加。这种最初的增加之后是一个衰减的增长率。然而，关于CD4水平对抗逆转录病毒治疗的反应仍有许多问题。通过检查自治疗开始以来的中位数CD4细胞计数，线性混合模型或广义线性模型，分析了抗逆转录病毒治疗的CD4反应。这些方法提供了研究样本中的一般CD4反应模式。然而，在开始抗逆转录病毒治疗的人群中，可能存在其他模式，更复杂的个体反应模式。我们假设个体的反应模式可能聚集在几种不同的反应模式类型中，如有效反应者（CD4迅速增加，达到正常水平），无效反应者（CD4缓慢增加，低于正常水平），无反应者（CD4稳定或缓慢增加），间歇性反应者（有反应但随后减少的个体），以及其他潜在的反应模式。此外，CD4水平在开始有效治疗后是否处于正常或低于正常水平的问题仍然没有答案。这些知识上的差距阻碍了对成功免疫反应定义的制定，因为目前的艾滋病毒指南只提供了广泛的指导。这些指导方针指出，治疗的目标是恢复和保持免疫功能，但没有概述在实现可获得的CD4计数方面的具体目标。因此，对有效抗逆转录病毒治疗的全球免疫反应：CD4 （GiREAT:CD4）的目标是：1)确定对抗逆转录病毒治疗的典型CD4反应模式，并确定这些模式的潜在预测因素，包括预测未来CD4反应的基于网络的工具；2)制作类似儿童生长图的CD4反应图，作为提供者的工具，识别CD4增长衰减率和CD4平台水平；3)确定CD4反应模式和个体反应与全因死亡率和病因特异性死亡率的关系。将在全球7个区域检查CD4对抗逆转录病毒治疗反应的这些差异，以确定是否存在区域反应差异。GiREAT:CD4将嵌套在评价艾滋病国际流行病学数据库（IeDEA）内，该数据库是由国家过敏和传染病研究所建立的七个区域中心组成的国际研究联盟。伟大：CD4采取了一种创新的新方法来检查CD4水平如何对ART的启动作出反应的问题。这将通过使用新的分析方法以及通过发展新的统计方法来实现。通过great:CD4收集的信息将确定对抗逆转录病毒治疗的成功免疫反应，从而改善对艾滋病毒感染者的临床护理。

DESCRIPTION (provided by applicant): CD4 cell counts have been shown to initially increase sharply in response to the initiation of effective antiretroviral therapy (ART). This initial increse is then followed by an attenuated rate of increase. However, many questions remain regarding how CD4 levels respond to ART. CD4 response to ART has been analyzed by examining the median CD4 cell count over time since the initiation of treatment, linear mixed models, or generalized linear models. These approaches provide the general CD4 response pattern in the study sample. Yet other patterns, more complex patterns in individual response are likely to be present within a population initiating ART. We hypothesize that an individual's response pattern may cluster within several distinct response pattern types such as effective responders (quickly increase in CD4 which plateaus at normal CD4 levels), ineffective responders (slowly increase in CD4 and plateaus below normal), non-responders (CD4 is stable or very slowly increases), intermittent responders (individuals who respond but then decrease), as well as other potential response patterns. Additionally, the question of whether CD4 levels after the initiation of effective treatment plateau at normal or below normal levels remains unanswered. These gaps in knowledge hinder the development of a definition of successful immune response as current HIV guidelines only give broad guidance. These guidelines state that the goal of treatment is to restore and preserve immunologic function but do not outline a specific objective in terms of achieving an obtainable CD4 count. Therefore the goal of the Global immunological Response to Effective Antiretroviral Therapy: CD4 (GiREAT:CD4) is to 1) identify typical CD4 patterns of response to ART and identify potential predictors of these patterns including a web-based tool for predicting future CD4 response; 2) Develop CD4 response charts which are analogous to children's growth charts as a tool for providers and identify the rate of attenuation of CD4 increase and the level of CD4 plateau; and 3) determine the association of CD4 response patterns and individual's response with all-cause and cause-specific mortality. These differences in CD4 response to ART will be examined across 7 global regions to determine if regional differences in response are present. GiREAT:CD4 will be nested within the International epidemiologic Database to Evaluate AIDS (IeDEA) an international research consortium of seven regional centers established by the National Institute of Allergy and Infectious Disease. GiREAT:CD4 takes an innovative fresh approach to examining the question of how CD4 levels respond to the initiation of ART. This will be achieved using novel analytical methods as well as through the development of new statistical methods. The information gleaned through GiREAT:CD4 will define a successful immune response to ART and thereby improve clinical care of HIV infected individuals.