Rapid Test for Recent HIV Infection and Incidence Panels for Assay Evaluation

描述（由申请人提供）：近期艾滋病毒感染快速检测和用于分析评估的发病率面板项目摘要对艾滋病毒发病率的准确估计是监测疫情、确定资源目标和评估各种干预措施有效性所必需的。然而，人们普遍认为，作为这些估计基础的分析是有缺陷的。这些缺陷包括：(1)缺乏对艾滋病毒亚型的一致的近期检测；(2)商业检测方法的可获得性不一致，这些检测方法已经过修改，以区分近期感染和长期感染；(3)迄今为止，在调整发生率方法以适应资源贫乏环境中可用的检测格式方面存在困难；(4)缺乏足够数量的发生率面板（来自具有密切估计感染日期的个体的血浆样本），以评估多种候选检测方法。在这个项目中，我们建议将血清学HIV发病率检测从目前的ELISA方法转变为可靠的横向流动快速检测格式，具有良好的覆盖所有HIV亚型和低误报率。这种快速检测将是稳定的、多色的、快速的、使用简单的，并且适用于各种HIV亚型占主导地位的人群。我们还计划开发纯种入射等离子体板，以评估这种新的测试方法；太阳能板将在世界范围内商业化。这些产品将基于三个关键资产：一种基于新型比色检测系统的新型高灵敏度快速检测技术，该技术允许在单个盒内分析抗体滴度和亲和力，将首次应用于艾滋病毒发病率检测；一种新的HIV抗原（rIDR-M），结合了与所有主要亚型相对应的免疫优势序列；以及一个经过验证的、经irb批准的方案，用于识别、招募和保留最近感染艾滋病毒的个体进行血液采集，以形成发病率小组。新的比色检测技术用于快速测试，在膜上产生明亮，高对比度，多色带。该方法的灵敏度远远超过常规胶体金或横向流动快速检测中使用的类似标签，也超过类似ELISA检测的灵敏度。新的快速测试方法将基于贪婪度，并已被证明可以区分事件样本和流行样本。同时生成的发病率面板将提供基本工具，用来描述快速试验以及其他候选发病率方法的性能。在第一阶段，我们预计将完成原型快速测试的开发和验证，并建立6个发病率血清组。将在第二阶段收集包括多个分支在内的额外样本，以支持商业版快速艾滋病毒发病率检测的最终开发和表征。

DESCRIPTION (provided by applicant): Rapid Test for Recent HIV Infection and Incidence Panels for Assay Evaluation Project Summary Accurate estimates of HIV incidence are required for monitoring the epidemic, for targeting resources, and for evaluating the effectiveness of various interventions. Yet the assays that underlie these estimates are widely understood to be flawed. Among the flaws are (1) the lack of consistent recency detection across HIV subtypes, (2) inconsistent availability of commercial test methods that have been modified to discriminate recent from long-standing infection, (3) difficulties to date in adapting incidence methods to test formats usable in resource-poor settings, and (4) lack of incidence panels (plasma samples from individuals with closely estimated infection dates) in sufficient volume for evaluation of multiple candidate assays. In this project, we propose to transform serological HIV incidence testing from the current ELISA methodology to a reliable lateral flow rapid test format with good coverage of all HIV subtypes and a low false recency rate. The rapid test will be stable, multi-colored, fast, simple to use, and applicable to populations where varyin HIV subtypes are dominant. We also plan development of pedigreed incidence plasma panels for evaluation of this new test method; panels will be made commercially available worldwide. These products will be based on three key assets: a new highly sensitive rapid test technology based on a novel colorimetric detection system, which allows for analysis of antibody titer and avidity within a single cassette, to be applied for the first time to an incidence test for HIV; a ew HIV antigen (rIDR-M) which combines immunodominant sequences corresponding to all major subtypes; and a proven, IRB-approved protocol for identifying, recruiting, and retaining recently HIV infected individuals for blood collections to form incidence panels. The new colorimetric detection technology for rapid test yields bright, high-contrast, multicolor bands on a membrane. The sensitivity of this method far exceeds that of conventional colloidal gold or similar labels used in lateral flow rapid tests, as well as exceeding the sensitivity of comparable ELISA assays. The new rapid test method will be based on avidity and has been demonstrated to distinguish between incident and prevalent samples. The incidence panels to be generated concurrently will provide the essential tool with which to characterize the performance of the rapid test as well as other candidate incidence methods. In Phase I, we expect to complete development and validation of a prototype rapid test and establish six incidence serum panels. Additional panels, including multiple clades, will be collected in Phase II to support final development and characterization of a commercial version of the rapid HIV incidence test.