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.

项目摘要 尽管在抗逆转录病毒疗法（ART）方面取得了成功的进步，但很大一部分 全世界都没有意识到他们的艾滋病毒感染。检测患有急性HIV感染的人至关重要，因为病毒 在出现可检测的HIV抗体之前，复制和脱落发生在此阶段。急性艾滋病毒的人 感染可以对HIV传播产生重大贡献。由于 耐药性和不遵守毒品。早期发现病毒反弹会显着影响该疾病 通过允许治疗干预并预防临床进展来管理。此外，治疗 中断已成为评估新疗法的至关重要的工具，以实现无艺术艾滋病毒的缓解。 但是，这些试验需要给参与者带来风险，可以通过更经常自我指导来缓解这种风险 病毒载荷监测。尽管具有敏感性和特异性，但核酸测试（NAT）无法实施 由于禁止的成本和对熟练运营商的需求而导致的护理点（POC）。当前基于抗体 POC技术，例如插件和酶联免疫测定（ELISA），无效检测 是艺术失败或急性艾滋病毒。已经表明，给定病毒RNA负载的P24抗原结果可能会有所不同， 这使得P24分析的值得信赖。此外，p24分析可能会由于 血清中P24特异性抗体的存在。那是立即需要易于使用的 在感染后的前两周，用于检测急性HIV的便携式且廉价的诊断工具， 在治疗中停用或耐药性后，病毒反弹。病毒负荷测试是 最准确和首选的艺术监测和急性HIV检测方法，并且高度 由WHO指南推荐，作为HIV管理和治疗监测的重要工具。到 解决这个重大的临床障碍，我们建议开发低成本，快速和敏感的光学系统 快速（<30分钟）检测急性HIV（感染后的前两周）和病毒反弹（终止后 使用指纹体积（<100 µL）的全血固定在廉价的，廉价的， 一次性和质量可实现的微流体装置。微技术和激增的进步 消费电子设备为开发移动健康（MHealth）技术铺平了坚实的基础 改变全球卫生中当前范式的潜力。智能手机可以无缝集成 借助硬件，软件和微流体，可以开发真正的POC诊断设备，以解决临床差距 艾滋病毒管理。