ACUTE HIV INFECTION AND EARLY DISEASE RESEARCH PROGRAM (AIEDRP)

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本方案的目的是建立一个参与HIV-1发病机制研究的HIV-1感染者队列，研究评估个体AIEDRP临床试验中的治疗策略；推迟治疗的受试者同意遵循本方案。入选受试者将根据急性或近期HIV-1感染情况在数据库中进行分层。这将使交叉方案分析能够解决与急性或近期HIV-1感染的发病机制和治疗有关的具体长期问题。登记的受试者可以为多种分析提供数据。该方案的主要目的是确定在急性或早期感染期间被诊断并立即开始治疗或延迟治疗直至慢性HIV-1疾病过程中某个未来点的受试者的长期病毒学，免疫学和临床结果和并发症。建立AIEDRP长期队列的基本原理是随着时间的推移继续跟踪和收集重要的结果，即使在受试者完成了有时间限制的临床试验或干预之后，这对于评估在急性和/或近期HIV-1感染的情况下进行的干预的长期影响将是重要的。参加本项目父方案的受试者也将共同参加本方案的数据收集。该方案要求提交基线访问、第2周、第4周、第12周以及此后每12周的数据，直到第168周（研究3年）。在研究期间，受试者将每24周访问一次。如果在研究期间的任何时间进行了额外的访问，CRFs存在的所有相关数据将提交给AIEDRP CORE01数据库。CORE01方案的总体目标是为急性和早期HIV-1感染患者提供统一的定义和就诊时间表，并将其输入临床数据库。AIEDRP CORE01数据库协议将建立一个HIV-1感染个体的队列，这些个体正在参与HIV-1发病机制的研究，在AIEDRP个体临床试验中评估治疗策略的研究，以及选择推迟治疗但同意遵循本协议的受试者。入选受试者将根据急性或近期HIV-1感染情况在数据库中进行分层。以明确的方式收集前瞻性数据将允许跨方案分析，以解决与急性或近期HIV-1感染的发病机制和治疗相关的特定长期科学问题。登记的受试者可以为多种分析提供数据。该方案的主要目的是确定在急性或早期HIV-1感染期间诊断并立即开始治疗或延迟治疗直至慢性HIV-1疾病过程中某个未来点的受试者的长期病毒学，免疫学和临床结果和并发症。AIEDRP目前或以前进行的发病机制和治疗干预临床试验的结果已经并将继续有助于我们了解HIV-1疾病的发病机制。然而，HIV-1发病机制的新进展，监测血浆和组织库中HIV-1复制的改进工具和机制的可用性，以及新型抗逆转录病毒疗法和治疗策略的发展，将需要对急性或近期感染的受试者进行持续评估。AIEDRP CORE01数据库协议将促进在AIEDRP各个单位进行的纵向和前瞻性计划的荟萃分析或跨协议分析，其中有关特定抗逆转录病毒或治疗性干预方案或策略的信息，使用新工具实时监测抗逆转录病毒效应和耐药性的发展，以及影响治疗反应的因素，以解决和比较急性或最近感染艾滋病毒1的个人管理的长期战略办法。本CORE01方案将为跨个别地点和方案评估长期战略问题提供框架，这些问题涉及初始治疗方案的比较、病毒载量或切换药物或药物组合的其他阈值的确定，以及药物暴露对治疗结果的贡献。与免疫保存和重建以及病原体特异性免疫有关的问题也可以在正在进行和评估的介入性战略和短期发病机制研究的背景下加以解决。在急性或近期感染的情况下，包括各种治疗干预措施在内的前瞻性纵向数据库的开发也将允许检查与各种临床结果相关的人口统计学和宿主特征。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this protocol is to establish a cohort of of HIV-1 infected individuals who are participating in studies of HIV-1 pathogenesis, studies evaluating theraputic strategies in individual AIEDRP clinical trials amp; subjects who defer therapy who agree to be followed in this protocol. Enrolled subjects will be stratified in the database with regard to acute or recent HIV-1 infection. This will allow cross protocol analysis to address specific long term questions related to the pathogenesis and treatment of acute or recent HIV-1 infection. Enrolled subjects may contribute data to multiple analyses. The primary aim of this protocol is to determine the long term virologic, immunologic an clinical outcomes and complications for subjects who were diagnosed during acute or early infection and who either begin therapy immediately, or defer therapy until some future point in the course of chronic HIV-1 disease. The rationale for establishing the AIEDRP long term cohort is to continue to follow and collect important outcomes over time, even after subjects have completed a time-limited clinical trial or intervention, will be important in evaluating the long-term impact of interventions that take place in the setting of acute and/or recent HIV-1 infection. Subjects who enroll in the parent protocol for this project will also co-enroll in this protocol for data collection. This protocol requires data to be submitted for baseline visit, weeks, 2, 4, 12, and every 12 weeks thereafter until week 168 (3 years on study), subjects will then have visits every 24 weeks for the duration of the study. If additional visits are made at any time during the study, all relevant data for which CRFs exist will be submitted to the AIEDRP CORE01 Data Base. The overall objective of the CORE01 protocol is to provide a uniform definition and schedule of visits for individuals with acute and early HIV-1 infection to be entered into a clinical database. The AIEDRP CORE01 Database Protocol will establish a cohort of HIV-1-infected individuals who are participating in studies of HIV-1 pathogenesis, studies evaluating therapeutic strategies in individual site AIEDRP clinical trials, and of subjects who choose to defer therapy but agree to be followed in this protocol. Enrolled subjects will be stratified in the database with regard to acute or recent HIV-1 infection. The collection of prospective data in a defined manner will allow cross-protocol analyses to address specific long-term scientific questions related to the pathogenesis and treatment of acute or recent HIV-1 infection. Enrolled subjects may contribute data to multiple analyses. The primary aim of this protocol is to determine the long-term virologic, immunologic, and clinical outcomes and complications for subjects who were diagnosed during acute or early HIV-1 infection and who either began therapy immediately, or defer therapy until some future point in the course of chronic HIV-1 disease. Results from the pathogenesis and therapeutic intervention clinical trials currently or previously conducted within the AIEDRP have contributed and continue to contribute to our understanding of the pathogenesis of HIV-1 disease. However, new developments in HIV-1 pathogenesis, the availability of improved tools and mechanisms for monitoring HIV-1 replication in plasma and tissue reservoirs, and the development of novel antiretroviral therapies and treatment strategies will require ongoing assessment of these in subjects with acute or recent infection. The AIEDRP CORE01 Database Protocol will facilitate longitudinal and prospectively planned meta-analyses or cross-protocol analyses of the studies conducted at individual AIEDRP units, in which information about specific antiretroviral or therapeutic intervention regimens or strategies, the use of new tools for real-time monitoring of antiretroviral effects and development of drug resistance, and factors that impact on treatment response will be performed to address and compare longer term strategic approaches to management of individuals acutely or recently infected with HIV-1. This CORE01 Protocol will provide the framework for evaluating across individual sites and protocols the longer term strategic questions regarding comparisons of initial treatment regimens, determination of viral load or other thresholds for switching a drug or combinations of drugs, and the contribution of drug exposure to treatment outcome. Questions related to immune preservation and reconstitution and pathogen-specific immunity can also be addressed in the context of the interventional strategies and short-term pathogenesis studies that are being conducted and evaluated. The development of a prospective, longitudinal database including a variety of therapeutic interventions in the setting of acute or recent infection will also permit examination of demographic and host characteristics that are associated with various clinical outcomes.