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: 10200655
• 负责人: Hadi Shafiee
• 金额: $ 53.7万
• 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 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10200655
• 关键词: Acquired Immunodeficiency Syndrome; Acute; Address; Affect; Aftercare; Antibodies; Antigens; 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 Reagent Kits; Disease; Disease Management; Disease remission; Drug resistance; Early Diagnosis; Electronics; Enzyme Immunoassay; Enzyme-Linked Immunosorbent Assay; Enzymes; Failure; Foundations; Guidelines; HIV; HIV Antibodies; HIV Infections; Hand; Human Herpesvirus 4; Human Herpesvirus 8; Human Papillomavirus; Human immunodeficiency virus test; Immunoassay; Individual; Infection; Interruption; Intervention; Label; Laboratory Technicians; Link; 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; Research; Resources; 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; base; clinically relevant; cost; data acquisition; diagnostic assay; 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; technology validation; tool; transmission process; trustworthiness; viral RNA; viral detection; viral rebound; virology

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.

项目摘要 尽管抗逆转录病毒疗法（ART）取得了成功，但仍有相当一部分人 全世界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 复制和脱落发生在可检测的HIV抗体出现之前的这个阶段。急性艾滋病毒感染者 感染可大大促进艾滋病毒传播。接受ART治疗的个体中可能发生病毒反弹， 耐药性和抗逆转录病毒疗法不依从性。早期发现病毒反弹可显著影响疾病 通过允许治疗干预和预防临床进展来管理。此外，治疗 中断治疗已成为评估新疗法以实现无ART HIV缓解的重要工具。 然而，这些试验给参与者带来了风险，这可以通过更频繁的自我指导来减轻。 病毒载量监测。尽管具有灵敏度和特异性，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，当前基于抗体的 POC技术，如试纸和酶联免疫测定法（ELISA），不能有效检测 抗逆转录病毒治疗失败或急性艾滋病毒感染。已经表明，给定病毒RNA载量的p24抗原结果可能不同， 这使得p24测定不太可信。此外，p24检测可能提供假阴性结果， 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， ART治疗中止或耐药后个体的病毒反弹。病毒载量检测是 是ART监测和急性HIV检测的最准确和首选方法， 世卫组织指南建议将其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、快速和灵敏的光学系统 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），使用手指针刺量（<100微升）的全血置于一个便宜的， 一次性的和可批量生产的微流体装置。微技术的进步和 消费电子产品为开发移动的健康（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 利用硬件、软件和微流体技术开发真正的POC诊断设备，以解决 艾滋病毒管理。