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: 10468751
• 负责人: Weihua Guan
• 金额: $ 41.17万
• 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 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10468751
• 关键词: AIDS/HIV problem; 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; Failure; Fingers; Guidelines; HIV; HIV Infections; HIV Seronegativity; HIV-1; 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; 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; base; cost effective; empowered; experience; high risk population; home test; improved; innovation; isothermal amplification; mortality; operation; performance tests; prevent; programs; prototype; public health relevance; recruit; research clinical testing; satisfaction; screening; self testing; sex; software development; time use; transmission process; treatment adherence; usability; viral RNA; 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.

项目总结/摘要 抗逆转录病毒治疗（ART）的进步显著降低了艾滋病毒的死亡率和发病率， 将病毒载量（VL）降低至不可检测的水平。最近修订的世卫组织指南强烈建议常规 VL测试，以监测ART依从性并尽量减少失败。为此，艾滋病毒自我检测是一个过程， 想知道艾滋病毒状况的个人收集样本，进行测试并私下解释结果， 已经成为一种授权的方法。虽然核酸检测（NAT）在集中式 病毒载量定量实验室，其在自我检测中的可用性尚未得到证明，由于样本 处理和测定复杂性。本计画旨在开发一个超小型USB的定量测试 一种检测病毒反弹的设备，这种设备简单到足以让外行在美国测试自己。 States. 该项目的R61阶段将开发基于全血的测试，可以定量评估 HIV-1 RNA浓度低至1000拷贝/毫升，这是世卫组织建议的确定 治疗失败。在aim 1中，我们将开发用于流线型和自动化血浆的一次性微流控芯片 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检测方法， 探索最小拷贝数敏感性。在目标3中，我们将整合定量USB分析仪硬件 并开发软件，以实现简单和强大的操作。在目标4中，我们将在BSL-2中验证原型测试 实验室使用HIV-1血浆样本掺入全血。 该项目的R33阶段将评估HIV内的测试性能、可用性和利益相关者需求。 宾夕法尼亚州立好时医疗中心的综合护理计划。在目标5中，建议的 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 使用者对HIV VL自我检测的经验、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手指穿刺血中提取的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，它有可能大大提高 艾滋病病毒感染者的治疗结果。潜在的变革能力保证了 与这个项目相关的挑战。

项目成果

Sensitive and specific CRISPR-Cas12a assisted nanopore with RPA for Monkeypox detection.

• DOI: 10.1016/j.bios.2023.115866
• 发表时间: 2023-11
• 期刊: Biosensors & bioelectronics
• 影响因子: 12.6
• 作者: Md. Ahasan Ahamed;Muhammad Asad Ullah Khalid;Ming Dong;Anthony J Politza;Zhikun Zhang;Aneesh Kshirsagar;Tianyi Liu;W. Guan

Sample-to-Answer Microfluidic Nucleic Acid Testing (NAT) on Lab-on-a-Disc for Malaria Detection at Point of Need.

• DOI: 10.1007/978-1-0716-1803-5_16
• 发表时间: 2022
• 期刊: Methods in molecular biology (Clifton, N.J.)

Rapid detection of novel coronavirus SARS-CoV-2 by RT-LAMP coupled solid-state nanopores.

• DOI: 10.1016/j.bios.2021.113759
• 发表时间: 2022-02-01
• 期刊: Biosensors & bioelectronics
• 影响因子: 12.6
• 作者: Tang Z;Nouri R;Dong M;Yang J;Greene W;Zhu Y;Yon M;Nair MS;Kuchipudi SV;Guan W
• 通讯作者: Guan W

Fingerpick Blood-Based Nucleic Acid Testing on A USB Interfaced Device towards HIV self-testing.

• DOI: 10.1016/j.bios.2022.114255
• 发表时间: 2022-08-01
• 期刊: Biosensors & bioelectronics
• 影响因子: 12.6

Digital CRISPR Systems for the Next Generation of Nucleic Acid Quantification.

• DOI: 10.1016/j.trac.2023.116917
• 发表时间: 2023-01
• 期刊: Trends in analytical chemistry : TRAC
• 作者: Anthony J Politza;Reza Nouri;W. Guan