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.

项目摘要/摘要 抗逆转录病毒治疗（ART）的进步显着降低了HIV的死亡率和发病率 将病毒载荷（VL）减少到无法检测到的水平。最近修订了谁指南强烈建议例行 VL测试以监测艺术依从性并最大程度地减少故障。为此，艾滋病毒自我测试，一个过程 想知道艾滋病毒状况的个人收集标本，执行测试并将结果解释为私人， 已成为一种授权的方法。虽然核酸测试（NAT）很容易在集中化中获得 用于病毒载荷量化的实验室，由于样本而尚未证明其自我测试的可用性 处理和分析复杂性。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，这很简单，以至于外行人可以在曼联测试自己 国家。 该项目的R61阶段将开发整个血液测试，可以定量评估存在 HIV-1 RNA的浓度低至1000份/毫升，建议确定的阈值 治疗失败。在AIM 1中，我们将开发一次性微流体芯片，用于流线型和自动化等离子体 分离和病毒RNA从全血中提取。在AIM 2中，我们将优化HIV-1 RT-LAMP测定法和 探索最小拷贝数灵敏度。在AIM 3中，我们将整合定量USB分析仪硬件 并开发软件，以便于易于操作。在AIM 4中，我们将验证BSL-2中的原型测试 实验室使用HIV-1等离子体样品掺入全血。 该项目的R33阶段将评估HIV中的测试绩效，可用性和利益相关者需求 宾夕法尼亚州赫尔希医学中心的综合护理计划。在AIM 5中，提议的表现 对HIV感染患者的测试将通过标准实验室方法进行基准测试。在AIM 6中，我们将评估 用户对HIV VL自我测试的经验，态度和看法。 通过微流体芯片和USB分析仪的创新，我们预计该测试能够量化 HIV-1 VL直接从100 µL手指刺血中直接低至1000份/ml。该项目的潜在影响 很高。如果该概念验证项目成功，它有可能显着增强 治疗中艾滋病毒个体的治疗结果。潜在的变革能力值得 与该项目相关的挑战。