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

对有效抗逆转录病毒治疗的整体免疫反应 (GiREAT:CD4)

• 批准号: 8693046
• 负责人: Bryan Lau
• 金额: $ 35.41万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8693046
• 关键词: Acquired Immunodeficiency Syndrome; American; Anti-Retroviral Agents; Attenuated; Body mass index; CD4 Lymphocyte Count; Categories; Characteristics; Child; Clinical; Complex; Computer software; Data; Databases; Development; Disease Progression; Epidemiology; European; Future; Glean; Goals; Growth; Guidelines; HIV; Heterogeneity; Immune response; Immune system; Immunologics; Individual; International; International AIDS; Knowledge; Linear Models; Methods; Modeling; National Institute of Allergy and Infectious Disease; Online Systems; Patients; Pattern; Population; Probability; Provider; RNA; Regimen; Reporting; Research; Research Infrastructure; Resources; Risk; Sampling Studies; Statistical Methods; Time; Weight; analytical method; antiretroviral therapy; attenuation; base; clinical care; clinical practice; effective therapy; follow-up; forest; improved; innovation; mortality; novel; regional difference; response; tool; treatment response

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.

描述（由申请人提供）：CD 4细胞计数已被证明在开始有效的抗逆转录病毒治疗（ART）后最初会急剧增加。这种最初的增长之后是一个衰减的增长率。然而，关于CD 4水平如何响应ART仍存在许多问题。通过检查自治疗开始以来随时间推移的中位CD 4细胞计数、线性混合模型或广义线性模型，分析了对ART的CD 4响应。这些方法提供了研究样本中的一般CD 4应答模式。然而，个体反应中的其他模式，更复杂的模式可能存在于启动ART的人群中。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，例如有效反应者（CD 4快速增加，在正常CD 4水平达到平台），无效应答者在一些实施方案中，免疫应答包括免疫应答（CD 4缓慢增加并低于正常水平）、无应答者（CD 4稳定或非常缓慢增加）、间歇性应答者（有应答但随后降低的个体）以及其他潜在应答模式。此外，在开始有效治疗后，CD 4水平是否稳定在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成功免疫反应定义的发展，因为目前的艾滋病毒指南只提供了广泛的指导。这些指南指出，治疗的目标是恢复和保护免疫功能，但没有概述实现可获得的CD 4计数方面的具体目标。因此，有效抗逆转录病毒疗法的全球免疫反应的目标：（GiREAT：CD 4）是1）确定对ART的典型CD 4反应模式，并确定这些模式的潜在预测因素，包括用于预测未来CD 4反应的基于网络的工具; 2）开发类似于儿童生长图表的CD 4反应图表，作为提供者的工具，并确定CD 4增加的衰减率和CD 4平台水平;和3）确定CD 4应答模式和个体应答与全因和特异性原因死亡率的关联。将在全球7个地区检查抗逆转录病毒治疗的CD 4应答差异，以确定是否存在应答的地区差异。GiREAT：CD 4将被嵌套在评估艾滋病的国际流行病学数据库（IeDEA）中，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。GiREAT：CD 4采取了一种创新的新方法来研究CD 4水平如何对ART的启动做出反应的问题。这将通过使用新的分析方法以及通过开发新的统计方法来实现。通过GiREAT：CD 4收集的信息将定义对ART的成功免疫应答，从而改善HIV感染者的临床护理。