Rapid Test for Recent HIV Infection

近期 HIV 感染快速检测

• 批准号: 8826016
• 负责人: Patricia E Garrett
• 金额: $ 100万
• 依托单位: IMMUNETICS, 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 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8826016
• 关键词: AIDS prevention; Acute; Africa; Antibodies; Antigens; Asia; Avidity; Biological Assay; Blood; Blood specimen; Botswana; Centers for Disease Control and Prevention (U.S.); Characteristics; Classification; Clinical Management; Collaborations; Country; Data; Dependence; Detection; Development; Devices; Diagnostic; Discrimination; Dissociation; Enzyme-Linked Immunosorbent Assay; Epidemic; Evaluation; Exhibits; Freeze Drying; Frequencies; Goals; Growth; HIV; HIV Envelope Protein gp41; HIV Infections; Health; Housing; Incidence; Individual; Infection; Instruction; Intervention; Kenya; Laboratories; Malawi; Membrane; Methodology; Methods; Modification; Monitor; Nigeria; Pattern; Peptides; Performance; Peripheral; Phase; Plasma; Policies; Population; Population Surveillance; Preparation; Prevalence; Procedures; Process; Public Health; Publications; RNA; Reading; Reproducibility; Research; Research Infrastructure; Research Institute; Resources; Running; Sampling; Sensitivity and Specificity; Series; Serological; Serum; Signal Transduction; Site; Specimen; Surveillance Methods; System; Tanzania; Technology; Testing; Thailand; Training; Tube; Validation; Viral Load result; Whole Blood; Work; base; design; effective intervention; instrumentation; novel; performance tests; prevent; prototype; repository; seroconversion; success; synthetic peptide; systems research; tool; transmission process; waiver

DESCRIPTION (provided by applicant): Monitoring the HIV epidemic to understand rates and patterns of growth, as well as targeting intervention efforts to populations exhibiting high rates f HIV transmission, are wholly dependent on determining the frequency of new infections using an assay that discriminates recent from long-term HIV infection. However, very few HIV assays have been developed specifically to distinguish incidence from prevalence. An added barrier has been the lack of an incidence assay for field work and resource-poor settings. Most HIV serologic assays are aimed at diagnostic use, while RNA assays have been used largely to determine viral load for clinical management purposes. Furthermore, HIV incidence testing currently requires access to well-equipped centralized laboratories capable of running the few sophisticated assays available for this purpose; these have been ELISAs requiring microplate handling and reading instrumentation, including the BED ELISA and the Vironostika detuned ELISA. Dependence on a central laboratory also implies the requirement for a system to transport serum specimens from where they have been collected to the laboratory, a separate and acute logistical challenge. In this project, we propose to transform HIV serological incidence testing from ELISA methodology based on avidity and titer and requiring a laboratory with sophisticated infrastructure, to a field procedure using a simple, stable, and reliable rapid test.In Phase I, we have developed prototypes of a new, highly sensitive rapid test based on novel colorimetric detection technology, which allows the analysis of antibody titer and avidity in less than 15 minutes within a single cassette. The rapid assay is based on synthetic peptides derived from a recently developed multisubtype gp41 HIV peptide antigen (IDR-M) which is the basis for the currently state-of- the-art limiting antigen (LAg) ELISA for incidence testing. Evaluated with a CDC incidence/prevalence panel, the prototype rapid assay yielded > 98% correlation with the LAg ELISA. In Phase II, we will evaluate the accuracy of the new rapid test for classification of recent vs. long-term HIV infections using well-characterized serum/plasma panels developed specifically for this purpose. These will include a panel representing recently HIV-infected individuals (HIV RNA positive/anti-HIV negative at recruitment) collected over a two year period as a specific aim in Phase I. Field evaluations of the rapid test will be carried ot in collaboration with public health agencies at global sites in low-resource regions to determine its performance characteristics and operability. The new rapid HIV incidence test will serve a major public health need by bringing testing to identify new HIV infections to the field, where the subject is located, enabling more efficient monitoring of the HIV epidemic at a local level and more effective intervention tactics.

描述（由申请人提供）：监测艾滋病毒的流行以了解其增长率和增长模式，以及针对艾滋病毒传播率高的人群进行有针对性的干预工作，完全依赖于使用一种区分近期和长期艾滋病毒感染的测定方法来确定新感染的频率。然而，专门用于区分发病率和流行率的艾滋病毒检测方法很少。另一个障碍是缺乏针对野外工作和资源贫乏环境的发病率分析。大多数艾滋病毒血清学检测的目的是用于诊断，而RNA检测主要用于确定临床管理目的的病毒载量。此外，艾滋病毒发病率检测目前需要使用设备良好的集中实验室，能够进行为数不多的为此目的提供的复杂分析；这些酶联免疫吸附试验需要微孔板处理和读取仪器，包括BED酶联免疫吸附试验和Vironostika失调谐酶联免疫吸附试验。对中心实验室的依赖还意味着需要一个系统将血清标本从采集地运送到实验室，这是一个单独的、严峻的后勤挑战。在这个项目中，我们建议将HIV血清学发病率检测从基于亲和力和滴度的ELISA方法（需要具有复杂基础设施的实验室）转变为使用简单、稳定和可靠的快速检测的现场程序。在第一阶段，我们开发了一种基于新型比色检测技术的新型高灵敏度快速测试的原型，该测试可以在不到15分钟的时间内在单个卡带内分析抗体滴度和亲和力。这种快速检测方法基于合成肽，该合成肽来源于最近开发的多亚型gp41 HIV肽抗原（IDR-M），这是目前最先进的用于发病率检测的限制性抗原（LAg） ELISA的基础。通过CDC发病率/患病率面板进行评估，原型快速检测与LAg ELISA的相关性为bb0.98%。在第二阶段，我们将使用专门为此目的开发的具有良好特征的血清/血浆面板，评估用于近期与长期HIV感染分类的新型快速检测的准确性。其中将包括一个代表最近感染艾滋病毒的个人（征聘时艾滋病毒RNA阳性/抗艾滋病毒阴性）的小组，作为第一阶段的具体目标，在两年期间收集。将与资源匮乏地区的全球站点的公共卫生机构合作，对快速检测进行实地评估，以确定其性能特点和可操作性。新的艾滋病毒发病率快速检测将满足一项重大的公共卫生需求，因为它将检测方法用于确定新的艾滋病毒感染