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

描述(由申请人提供)：最近艾滋病毒感染的快速检测和检测评估项目总结的发病率小组需要准确估计艾滋病毒发病率，以监测疫情，确定资源，并评估各种干预措施的有效性。然而，支撑这些估计的分析被广泛认为是有缺陷的。其中的缺陷包括(1)缺乏对艾滋病毒亚型的一致的新近检测，(2)商业检测方法的可用性不一致，这些方法已被修改以区分最近和长期的感染，(3)迄今在调整发病率方法以适应资源匮乏环境中可用的检测格式方面存在困难，以及(4)缺乏足够数量的发病率小组(来自感染日期密切估计的个人的血浆样本)来评估多种候选检测。在这个项目中，我们建议将血清学HIV发病率检测方法从目前的ELISA法转变为可靠的横向流动快速检测模式，具有良好的覆盖所有HIV亚型的能力和较低的假复发率。该快速检测将是稳定的，多颜色，快速，使用简单，适用于各种HIV亚型占主导地位的人群。我们还计划开发谱系关联等离子体面板，以评估这种新的测试方法；面板将在全球范围内商业化。这些产品将基于三项关键资产：基于新型比色检测系统的新的高灵敏快速检测技术，该技术允许在单个试剂盒内分析抗体效价和亲和力，首次应用于艾滋病毒的发病率测试；一种新的艾滋病毒抗原(rIDR-M)，它结合了与所有主要亚型对应的免疫显性序列；以及一种经过验证的、IRB批准的协议，用于识别、招募和保留最近感染艾滋病毒的人进行血液采集，以形成发病率小组。用于快速检测的新比色检测技术在薄膜上产生明亮、高对比度、多色的条带。该方法的灵敏度远远超过传统的胶体金或类似的标记用于侧向流动快速检测，也超过了可比的ELISA法的灵敏度。新的快速检测方法将以亲和力为基础，并已被证明可以区分事故样本和流行样本。将同时生成的关联小组将提供必要的工具，用于表征快速测试以及其他候选关联方法的性能。在第一阶段，我们希望完成原型快速测试的开发和验证，并建立六个关联血清试剂盒。将在第二阶段收集更多的小组，包括多个分支，以支持最后开发和确定快速艾滋病毒发病率快速检测商业版本的特征。

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.