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）抗逆转录病毒疗法（ART）的革命性进展可以 达到并维持病毒抑制已逐渐转变为艾滋病毒/获得性免疫缺陷综合症 在过去的二十年里，艾滋病（AIDS）变成了一种可控制的慢性疾病。但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综合战略 针对艾滋病毒，世界卫生组织 (WHO) 特别呼吁不仅要提高抗逆转录病毒治疗的可及性，而且要提高艾滋病治疗的可及性 HIV 检测旨在覆盖未经检测的高危人群，并帮助 PLWHA 确定其病毒载量 (VL) 和 传播潜力。作为回应，该项目旨在开发一种诊断技术，以实现快速、经济的诊断 易于使用的 HIV VL 检测，适合自我检测甚至家庭检测。与传统的不同 由于复杂设备的要求，诊断技术对于自测试来说不切实际 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传输 操作，实现样品处理和 PCR 的集成，无需复杂的流体 墨盒和配套仪器。仪器和测定的小型化 磁流体技术最大限度地减少了试剂消耗和热质量，从而使成本和成本降低了 10 倍以上 测定时间。该集成设备有利于从指尖采血中检测 HIV RNA，以一种简单的“样本到 答案”的方式，承诺一种快速、廉价且用户友好的 VL 自测试策略。 我们组建了一支多学科团队，具有互补的专业知识和良好的业绩记录和历史 团队科学中的合作。为了实现上述目标，我们建议（i）制定一个精简的 用于样品处理和全血中 HIV 的 PCR 检测的测定方案，(ii) 开发一种廉价的 磁流体盒将 HIV 检测分析作为简单的血液结果测试，(iii) 开发 便携式仪器，以实现简便的 HIV 自检，(iv) 开发一种环境盒存储方法，以及 最后 (v) 评估 HIV 自检平台在急症护理中的性能和患者可接受性 和资源有限的设置。这种 HIV VL 自检技术的开发具有潜力 大大提高了感染者中检测急性感染和监测病毒抑制的可及性， 从而改变了全球艾滋病毒预防战略的游戏规则。