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

最近 HIV 感染的快速检测和用于分析评估的发病率小组

• 批准号: 8409988
• 负责人: Russell k Garlick
• 金额: $ 29.98万
• 依托单位: SERACARE LIFE SCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-15 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8409988
• 关键词: Achievement; Aliquot; Anti-Retroviral Agents; Antibodies; Antigens; Avidity; Biological Assay; Blood; Cells; Clinic; Collaborations; Collection; Color; Communicable Diseases; Detection; Development; Development Plans; Diagnostic; Discrimination; Dissociation; Effectiveness; Enzyme-Linked Immunosorbent Assay; Epidemic; Evaluation; Gold Colloid; HIV; HIV Antibodies; HIV Antigens; HIV Envelope Protein gp41; HIV Infections; Human immunodeficiency virus test; Incidence; Individual; Infection; Institutional Review Boards; Intervention; Label; Laboratories; Lateral; M cell; Marketing; Membrane; Methodology; Methods; Monitor; Participant; Peptides; Performance; Phase; Plasma; Plasma Cells; Policies; Population; Population Heterogeneity; Population Surveillance; Prevalence; Procedures; Process; Protocols documentation; Public Health; RNA; Recruitment Activity; Research Infrastructure; Research Personnel; Resources; Sampling; Sensitivity and Specificity; Series; Serological; Serum; System; Technology; Testing; Time; Validation; Work; base; innovation; next generation; novel; performance tests; prototype; tool

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. PUBLIC HEALTH RELEVANCE: Rapid Test for Recent HIV Infection and Incidence Panels for Assay Evaluation Project Narrative SeraCare and Immunetics propose jointly to develop a new, rapid HIV incidence test for discrimination of recent vs. past infections by all HIV subtypes worldwide. Incidence/prevalence panels of well-characterized plasma from recently HIV infected individuals will be collected for use in qualifying this assay and will be made available commercially to other investigators and test developers. Development of a rapid and reliable test for recent HIV infection is a critical public health need for accurate determination of HIV incidence and will allow epidemiologists and researchers to understand whether HIV infection is increasing, decreasing, or staying level within a given population, greatly advancing the monitoring of interventions to reduce the spread of HIV worldwide.

描述（由申请人提供）：快速检测最近的艾滋病毒感染和发病率面板的检测评价项目摘要准确估计艾滋病毒的发病率需要监测流行病，有针对性的资源，并评估各种干预措施的有效性。然而，人们普遍认为，这些估计所依据的分析是有缺陷的。这些缺陷包括：（1）对艾滋病毒亚型缺乏一致的近因检测，（2）商业检测方法的可用性不一致，这些方法经过修改以区分近期感染和长期感染，（3）迄今为止，在使发病率方法适应可用于资源匮乏环境的检测格式方面存在困难，和（4）缺乏足够体积的发病率组（来自具有密切估计的感染日期的个体的血浆样品）以用于评价多个候选测定。 在这个项目中，我们建议将目前的ELISA方法的血清学HIV发病率检测转换为一个可靠的侧流快速检测格式，具有良好的覆盖率，所有的HIV亚型和低的假近率。快速检测将是稳定的，多色的，快速的，使用简单的，并适用于各种HIV亚型占主导地位的人群。我们还计划开发血统发病率血浆面板，用于评估这种新的测试方法;面板将在全球范围内上市。 这些产品将基于三个关键资产：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合力，首次应用于艾滋病毒的发病率检测;新型艾滋病毒抗原（rIDR-M），其结合了对应于所有主要亚型的免疫显性序列;以及经IRB批准的用于识别、招募和保留最近感染HIV的个体以进行血液采集以形成发病率组的经证实的方案。 用于快速检测的新比色检测技术在膜上产生明亮、高对比度、透明的条带。这种方法的灵敏度远远超过了传统的胶体金或类似的标签中使用的侧向流快速测试，以及超过了灵敏度可比的ELISA测定。新的快速检测方法将以亲合力为基础，并已被证明可以区分事件样本和流行样本。同时生成的发生率样本组将提供基本工具，用于表征快速检测以及其他候选发生率方法的性能。在第一阶段，我们预计将完成原型快速测试的开发和验证，并建立六个发病血清面板。将在II期收集包括多个进化枝在内的其他样本组，以支持HIV发病率快速检测试剂盒商业版本的最终开发和表征。 公共卫生关系：用于检测评估项目的近期HIV感染快速检测和发病率面板Narrative SeraCare和Immunetics共同提议开发一种新的快速HIV发病率检测，用于区分全球所有HIV亚型的近期与既往感染。将采集近期HIV感染个体的已充分表征血浆的发病率/患病率样本组，用于鉴定本检测试剂盒，并将向其他研究者和检测开发人员提供市售样本。开发一种快速、可靠的艾滋病毒感染检测方法是准确确定艾滋病毒发病率的关键公共卫生需求，将使流行病学家和研究人员了解艾滋病毒感染是否在特定人群中增加、减少或保持水平，大大推进对减少艾滋病毒全球传播的干预措施的监测。