Home Fingerprick Blood-Based HIV Self-Test For Quantitative Monitoring Of Viral Rebound

首页 指尖采血 HIV 自检，定量监测病毒反弹

• 批准号: 10878026
• 负责人: Weihua Guan
• 金额: $ 70.07万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10878026
• 关键词: Acquired Immunodeficiency Syndrome; Adherence; Age; Ambulatory Care Facilities; Antibody Response; Attitude; Awareness; Benchmarking; Benefits and Risks; Biological Assay; Blood; Blood Glucose; Blood specimen; Comprehensive Health Care; Data; Detection; Devices; Diagnostic tests; Drug resistance; Early Diagnosis; Electronics; Failure; Fingers; Guidelines; HIV; HIV Infections; HIV Seronegativity; HIV-1; HIV/AIDS; Health; Home; Hybrids; Individual; Infection; Laboratories; Lateral; Learning; Mechanics; Mediating; Medical center; Methods; Microfluidic Microchips; Microfluidics; Monitor; Morbidity - disease rate; Nucleic Acid Amplification Tests; Optics; Outcome; Participant; Patients; Perception; Performance; Persons; Phase; Plasma; Play; Population; Preparation; Privatization; Process; Public Health; RNA; Rapid diagnostics; Recommendation; Recovery; Reporting; Research; Reverse Transcription; Sampling; Sensitivity and Specificity; Side; Specimen; Surveys; Testing; Training; Treatment Failure; Treatment outcome; United States; Validation; Viral Load result; Viral load measurement; Virus; Whole Blood; antiretroviral therapy; cost effective; empowerment; experience; high risk population; home test; improved; innovation; isothermal amplification; manufacture; mortality; operation; performance tests; prevent; programs; prototype; public health relevance; recruit; research clinical testing; satisfaction; screening; self testing; sex; software development; transmission process; treatment adherence; usability; viral RNA; viral detection; viral rebound

Project Summary/Abstract The advancement of antiretroviral treatment (ART) has significantly reduced the HIV mortality and morbidity by reducing the viral load (VL) to undetectable levels. Recently revised WHO guidelines strongly recommend routine VL testing to monitor ART adherence and minimize failure. To this end, HIV self-testing, a process in which individual who wants to know HIV status collects a specimen, performs a test and interprets the result in private, has become an empowering approach. While nucleic acid testing (NAT) is readily available in centralized laboratories for viral load quantification, its availability in self-testing has not been demonstrated due to sample processing and assay complexity. This project aims to develop a quantitative test on an ultra-compact USB device to detect viral rebound that is simple enough for laypersons to test themselves in the United States. The R61 phase of the project will develop the whole blood-based test that can quantitatively assess the presence of HIV-1 RNA at concentrations as low as 1000 copies/ml, threshold recommended by WHO for determining treatment failure. In aim 1, we will develop a disposable microfluidic chip for streamlined and automated plasma separation and viral RNA extraction from whole blood. In aim 2, we will optimize the HIV-1 RT-LAMP assay and explore the minimum copy number sensitivity. In aim 3, we will integrate the quantitative USB analyzer hardware and develop software for easy and robust operation. In aim 4, we will validate the prototyped test in the BSL-2 lab using HIV-1 plasma samples spiked into whole blood. The R33 phase of the project will assess the test performance, usability and stakeholder needs within the HIV Comprehensive Care Program at Penn State Hershey Medical Center. In aim 5, the performance of the proposed test on HIV-infected patients will be benchmarked with standard laboratory methods. In aim 6, we will evaluate the user’s experience, attitude and perception of HIV VL self-testing. Through innovations in microfluidic chips and the USB analyzer, we anticipate the test would be able to quantify HIV-1 VL as low as 1000 copies/ml directly from 100 µl of finger prick blood. The potential impact of this project is very high. If this proof-of-concept project is successful, it has the potential to significantly enhance the treatment outcomes for individuals of HIV under therapy. The potential transformative capacity warrants the challenges associated with this project.

项目概要/摘要 抗逆转录病毒治疗（ART）的进步显着降低了艾滋病毒死亡率和发病率 将病毒载量（VL）降低至不可检测的水平。最近修订的世界卫生组织指南强烈建议常规 VL 测试可监测 ART 依从性并最大限度地减少失败。为此，艾滋病毒自我检测是一个过程 想要了解艾滋病毒状况的个人可以私下采集样本、进行测试并解释结果， 已成为一种赋权方法。虽然核酸检测 (NAT) 可以在集中进行 实验室进行病毒载量定量，但由于样本原因，其自检可用性尚未得到证实 处理和分析的复杂性。该项目旨在对超紧凑型 USB 进行定量测试 检测病毒反弹的设备对于非专业人士来说足够简单，可以在美国进行自我测试 国家。 该项目的R61阶段将开发基于全血的测试，可以定量评估是否存在 HIV-1 RNA 浓度低至 1000 拷贝/毫升，这是世界卫生组织推荐的测定阈值 治疗失败。在目标 1 中，我们将开发一种一次性微流控芯片，用于简化和自动化血浆 从全血中分离和提取病毒RNA。在目标 2 中，我们将优化 HIV-1 RT-LAMP 检测并 探索最小拷贝数敏感性。在目标3中，我们将集成定量USB分析仪硬件 并开发软件以实现简单、稳健的操作。在目标 4 中，我们将验证 BSL-2 中的原型测试 实验室使用掺入全血的 HIV-1 血浆样本。 该项目的 R33 阶段将评估 HIV 领域的测试性能、可用​​性和利益相关者需求 宾夕法尼亚州立大学好时医疗中心的综合护理计划。在目标 5 中，拟议的绩效 对艾滋病毒感染者的检测将以标准实验室方法为基准。在目标 6 中，我们将评估 用户对 HIV VL 自检的体验、态度和看法。 通过微流控芯片和 USB 分析仪的创新，我们预计该测试将能够量化 直接从 100 µl 指尖采血中检测到的 HIV-1 VL 低至 1000 拷贝/ml。该项目的潜在影响 非常高。如果这个概念验证项目成功，它有可能显着增强 接受治疗的艾滋病毒感染者的治疗结果。潜在的变革能力保证了 与该项目相关的挑战。