Streamlined 15-min HIV Viral Load Self-Testing Using Finger-Stick Blood

使用指尖采血进行简化的 15 分钟 HIV 病毒载量自检

• 批准号: 10878023
• 负责人: Yu-Hsiang Hsieh
• 金额: $ 75.36万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 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/10878023
• 关键词: AIDS prevention; Acceleration; Accident and Emergency department; Accreditation; Acquired Immunodeficiency Syndrome; Acute; Baltimore; Biological Assay; Blood; Buffers; Cellular Phone; Cessation of life; Charge; Chronic Disease; Clinic; Clinic Visits; Clinical; Clinical Management; Cold Chains; Collaborations; Communicable Diseases; Complex; Consent; Consumption; Detection; Development; Devices; Drug resistance; Early Diagnosis; FDA approved; Failure; Filtration; Fingers; Fluorescence; Freeze Drying; Goals; HIV; HIV Infections; Health Policy; Human immunodeficiency virus test; Hydration status; Infection; Interruption; Intervention; Laboratories; Liquid substance; Magnetism; Manuals; Membrane; Methods; Microfluidics; Miniaturization; Monitor; Patients; Performance; Persons; Phase; Plasma; Preparation; Prevention strategy; Process; Protocols documentation; Public Health; RNA; RNA purification; Reaction; Reagent; Recording of previous events; Resource-limited setting; Sampling; Schedule; Science; Self Administration; Site; Surveys; Techniques; Technology; Test Result; Testing; Time; Training; Translating; Uganda; Venipunctures; Viral; Viral Load result; Visit; Waxes; Whole Blood; World Health Organization; acute care; acute infection; amplification detection; antiretroviral therapy; cost; detection assay; detection limit; diagnostic technologies; high risk population; home test; improved; instrument; instrumentation; manufacture; miniaturize; multidisciplinary; novel; nucleic acid purification; operation; particle; portability; prevent; reconstitution; resistance mutation; response; seal; self testing; tool; transmission process; user-friendly; validation studies; viral rebound

The revolutionary advances in human immunodeficiency virus (HIV) antiretroviral therapy (ART) which could reach and maintain viral suppression have gradually transitioned HIV/acquired immunodeficiency syndrome (AIDS) to a manageable, chronic disease in the past 2 decades. However, it is still one of the leading public threats in the world with approximately 37.9 million people living with HIV (PLWHA), 1.7 million new infections, and 770,000 HIV-related deaths in 2018. As a comprehensive strategy for improving the clinical management of HIV, the World Health Organization (WHO) specifically calls for improved accessibility of not only ART, but also HIV testing to reach untested high-risk populations and to help PLWHA ascertain their viral load (VL) and potential for transmission. In response, this project seeks to develop a diagnostic technology for rapid, affordable and easy-to-use HIV VL detection that is amenable for self-testing and even in-home testing. Unlike conventional diagnostic technologies that are impractical for self-testing due to requirements of sophisticated devices and instruments, our platform employs magnetofluidic technology to replace bulk fluid transport with magnetic particle manipulation, enabling the integration of sample processing and PCR without the need for complex fluidic cartridges and supporting instrumentation. Miniaturization of instrumentation and assay facilitated by magnetofluidics minimizes reagent consumption and the thermal mass, leading to >10-fold reduction in cost and assay time. The integrated device facilitates HIV RNA detection from finger-stick blood in a facile “sample-to- answer” manner, promising a rapid, inexpensive and user-friendly strategy for VL self-testing. We have assembled a multi-disciplinary team with complementary expertise and strong track record and history of collaboration in team science. In order to achieve the above goal, we propose (i) to develop a streamlined assay protocol for sample processing and PCR detection of HIV in whole blood, (ii) to develop an inexpensive magnetofluidic cartridge implementing the HIV detection assay as a simple blood-to-result test, (iii) to develop a portable instrument to enable facile HIV self-testing, (iv) to develop a method for ambient cartridge storage, and finally (v) to evaluate performance and patient acceptability of the HIV self-testing platform in both acute care and resource-limited settings. The development of this HIV VL self-testing technology has the potential for dramatically increasing the accessibility of detecting acute infections and monitoring viral suppression in PLWHA, thus presenting a game changer in the global HIV prevention strategy.

人类免疫缺陷病毒（HIV）抗逆转录病毒治疗（ART）的革命性进展， 达到和维持病毒抑制已逐渐过渡到艾滋病毒/获得性免疫缺陷综合征 在过去的20年里，艾滋病（艾滋病）成为一种可控制的慢性疾病。然而，它仍然是领先的公众之一， 全球约有3790万艾滋病毒感染者（PLWHA），170万新感染者， 2018年有770，000例艾滋病毒相关死亡。作为改善临床管理的一项综合战略， 艾滋病毒，世界卫生组织（世卫组织）特别呼吁不仅要改善ART的可及性， * 艾滋病毒检测，以覆盖未经检测的高危人群，并帮助艾滋病毒感染者/艾滋病患者确定其病毒载量， 传播的可能性。作为回应，该项目旨在开发一种诊断技术， 和易于使用的HIV VL检测，适合自我检测，甚至在家中检测。不同于常规 由于复杂设备的要求而无法进行自检的诊断技术， 仪器，我们的平台采用磁流体技术，用磁性颗粒代替大量流体输送 操作，使样品处理和PCR的集成，而不需要复杂的流体 弹药筒和配套仪器。仪器和分析的小型化 磁流体最大限度地减少了试剂消耗和热质量，导致成本降低>10倍， 测定时间。该集成设备有助于从手指针刺血液中检测HIV RNA， 回答”的方式，承诺一个快速，廉价和用户友好的策略VL自我测试。 我们组建了一支多学科团队，拥有互补的专业知识和强大的业绩记录和历史 团队科学中的合作。为达致上述目标，我们建议（i）制订一套精简的 用于全血中HIV的样品处理和PCR检测的测定方案，（ii）开发廉价的 磁流体盒实现HIV检测测定作为简单的血液-结果测试，（iii）开发用于HIV检测的磁流体盒， 便携式仪器，使艾滋病毒的自我检测，（iv）开发一种方法，为环境盒储存，和 最后（v）评估HIV自测平台在急性护理和急性护理中的性能和患者可接受性 和资源有限的环境。这种HIV VL自我检测技术的发展有可能 大大增加了检测急性感染和监测艾滋病毒/艾滋病感染者的病毒抑制的可及性， 从而改变了全球艾滋病预防战略。