A mobile health diagnostic device for HIV self-testing

用于艾滋病毒自检的移动健康诊断设备

• 批准号: 10684287
• 负责人: Hadi Shafiee
• 金额: $ 89.31万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-09 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10684287
• 关键词: Acquired Immunodeficiency Syndrome; Acute; Address; Affect; Aftercare; Antibodies; Antigens; Antiretroviral drug resistance; Biological Assay; Blood Volume; Blood specimen; CD4 Lymphocyte Count; Cellular Phone; Cessation of life; Clinical; Computer software; Cytomegalovirus; Data Analyses; Detection; Developing Countries; Devices; Diagnosis; Diagnostic; Diagnostic Equipment; Diagnostic Reagent Kits; Disease; Disease Management; Disease remission; Drug resistance; Early Diagnosis; Electronics; Eligibility Determination; Enzyme Immunoassay; Enzyme-Linked Immunosorbent Assay; Failure; Fingers; Foundations; Guidelines; HIV; HIV Antibodies; HIV Infections; Human Herpesvirus 4; Human Herpesvirus 8; Human Papillomavirus; Human immunodeficiency virus test; Individual; Infection; Interruption; Intervention; Label; Laboratory Technicians; Methods; Microfluidic Microchips; Microfluidics; Monitor; Nanotechnology; Nucleic Acid Amplification Tests; Optical Readers; Optics; Participant; Pathogen detection; Patients; Performance; Persons; Phase; Platinum; Point of Care Technology; Policies; Recommendation; Research; Resource-limited setting; Risk; Saliva; Sampling; Self Direction; Seminal fluid; Sensitivity and Specificity; Serum; Signal Transduction; Simplexvirus; Solid; System; Technology; Telephone; Testing; Treatment Failure; Update; Urine; Venipunctures; Viral Load result; Virus; Virus Replication; Virus Shedding; Whole Blood; Work; World Health Organization; antiretroviral therapy; clinically relevant; cost; data acquisition; diagnostic assay; diagnostic tool; experience; global health; high reward; high risk; image processing; laboratory facility; lateral flow assay; low and middle-income countries; mHealth; microchip; mortality; nanoparticle; novel therapeutics; optical sensor; point of care; point-of-care detection; point-of-care diagnostics; portability; prevent; self testing; skills; technology validation; tool; transmission process; trustworthiness; viral RNA; viral detection; viral rebound

PROJECT SUMMARY Despite successful advancements in antiretroviral therapy (ART), a significant proportion of individuals worldwide are unaware of their HIV-infection. Detecting persons with acute HIV infection is crucial since viral replication and shedding occur in this stage before detectable HIV antibodies appear. Persons with acute HIV infection can contribute substantially to HIV transmission. Viral rebound in individuals on ART can occur due to drug resistance and ART non-adherence. Early detection of viral rebound can significantly affect the disease management by allowing treatment intervention and preventing clinical progression. Furthermore, treatment interruption has become a vital tool in the assessment of new therapies for achieving ART-free HIV remission. However, these trials entail risks to the participants, which could be mitigated with more frequent self-directed viral load monitoring. Despite the sensitivity and specificity, nucleic acid testing (NAT) cannot be implemented at the point-of-care (POC) due to prohibitive cost and demand for skilled operators. Current antibody-based POC technologies, such as dipsticks and enzyme-linked immunoassays (ELISA), are not effective to detect either ART failure or acute HIV. It has been shown that p24 antigen results for a given viral RNA load may vary, which makes p24 assays less trustworthy. In addition, p24 assays may provide false-negative results due to the presence of p24-specific antibodies in serum. Thus, there is an immediate need for an easy-to-use, portable, and inexpensive diagnostic tool for detecting acute HIV during the first two weeks after infection and viral rebound in individuals on ART after treatment discontinuation or drug resistance. Viral load testing is the most accurate and preferred approach for ART monitoring and acute HIV detection, and is highly recommended by WHO guidelines as an important tool for HIV management and treatment monitoring. To address this significant clinical barrier, we propose to develop a low-cost, rapid, and sensitive optical system for rapid (<30 min) detection of acute HIV (first two weeks after infection) and viral rebound (after terminating ART or due to drug resistance) using fingerprick volume (<100 µL) of whole blood placed on an inexpensive, disposable, and mass-producible microfluidic device. The advances in microtechnologies and the surge in consumer electronics have paved a solid foundation for developing mobile health (mhealth) technologies with the potential to transform the current paradigm in global health. Smartphones can be seamlessly integrated with hardware, software, and microfluidics to develop a true POC diagnostic device to address clinical gaps in HIV management.

项目概要 尽管抗逆转录病毒疗法 (ART) 取得了成功的进展，但仍有相当一部分人 全世界的人都不知道自己感染了艾滋病毒。检测急性艾滋病毒感染者至关重要，因为病毒 在可检测到的艾滋病毒抗体出现之前，复制和脱落发生在这个阶段。急性艾滋病毒感染者 感染可极大地促进艾滋病毒传播。接受 ART 治疗的个体出现病毒反弹的原因可能是 耐药性和 ART 不依从性。及早发现病毒反弹可显着影响疾病 通过允许治疗干预和预防临床进展来进行管理。此外，治疗 中断已成为评估实现无 ART 艾滋病毒缓解的新疗法的重要工具。 然而，这些试验会给参与者带来风险，可以通过更频繁的自我指导来减轻风险 病毒载量监测。尽管具有敏感性和特异性，但核酸检测（NAT）无法实施 由于高昂的成本和对熟练操作员的需求，在护理点 (POC) 进行操作。目前基于抗体 POC 技术，例如试纸和酶联免疫分析 (ELISA)，无法有效检测 ART 失败或急性 HIV。研究表明，给定病毒 RNA 载量的 p24 抗原结果可能会有所不同， 这使得 p24 检测不太可信。此外，p24 检测可能会由于以下原因提供假阴性结果： 血清中存在 p24 特异性抗体。因此，迫切需要一种易于使用、 便携式、廉价的诊断工具，用于在感染后的前两周内检测急性艾滋病毒 接受 ART 治疗的个体在治疗停止或耐药后病毒反弹。病毒载量测试是 ART 监测和急性 HIV 检测最准确和首选的方法，并且高度 世界卫生组织指南推荐作为艾滋病毒管理和治疗监测的重要工具。到 为了解决这一重大的临床障碍，我们建议开发一种低成本、快速且灵敏的光学系统 用于快速（<30 分钟）检测急性 HIV（感染后前两周）和病毒反弹（终止后） ART 或由于耐药性）使用指尖体积（<100 µL）的全血放置在廉价的、 一次性且可大规模生产的微流体装置。微技术的进步和技术的激增 消费电子产品为开发移动健康（mhealth）技术奠定了坚实的基础 改变当前全球卫生模式的潜力。智能手机可以无缝集成 与硬件、软件和微流体技术一起开发真正的 POC 诊断设备，以解决临床空白 艾滋病毒管理。