Smartphone-based diagnostic for HIV self-testing

基于智能手机的 HIV 自检诊断

• 批准号: 9756313
• 负责人: Jacqueline Linnes
• 金额: $ 37.81万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-06 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9756313
• 关键词: Acquired Immunodeficiency Syndrome; Adopted; Adoption; Africa; Algorithms; Anthropology; Antibodies; Awareness; Biological Assay; Biosensor; Blood; Blood specimen; Car Phone; Cellular Phone; Chronic; Clinical; Clinical Research; Clinical Trials; Cost Savings; Data; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic tests; Diffusion; Ensure; Equipment; Evaluation; Fluorescence; Goals; Gold; HIV; HIV Infections; HIV Seropositivity; Hand; Health; Health Care Costs; Health Personnel; Healthcare; Human; Human immunodeficiency virus test; Immunoassay; Immunology; Indiana; Individual; Kenya; Label; Laboratories; Laboratory Technicians; Measures; Mediating; Medical; Methods; Microfluidic Microchips; Microfluidics; Microprocessor; Monitor; Motion; Nucleic Acids; Outcome; Pathogen detection; Patients; Performance; Phase; Plasma; Positioning Attribute; Power Sources; Preparation; Process; Quality of life; Reproducibility; Resolution; Running; Sampling; Sensitivity and Specificity; Technology; Testing; Time; United States; Universities; Viral; Viral Antigens; Viral Load result; Virus; Visit; Whole Blood; Work; amplification detection; antiretroviral therapy; barrier to care; base; care providers; clinically relevant; commercialization; compliance behavior; cost; design; holistic approach; improved; in vitro Assay; insight; interdisciplinary approach; intimate behavior; medical schools; molecular diagnostics; novel strategies; particle; pathogen; point of care; point-of-care diagnostics; prevent; prospective; prospective test; prototype; remote health care; scale up; smartphone Application; transmission process; usability; viral detection

SUMMARY ABSTRACT The 90-90-90 Target endorsed by UNAIDS, proposes diagnosing 90% of people infected with HIV worldwide, engaging 90% of them on effective antiretroviral treatment, and ensuring that 90% of those treated achieve sustained viral load suppression by 2020. The United States is woefully unprepared to reach this target; only 30% of HIV infected individuals in the U.S. currently achieve viral load suppression. Clearly, a paradigm shift in viral load testing will be required to accomplish this goal. This proposal aims to create a quantitative, handheld, viral load self-test that can be used by patients themselves to support their management of this chronic condition and that delivers relevant clinical insights to remote healthcare providers. Building on our preliminary work, the objective of the R61 phase is to combine isothermal loop- mediated nucleic acid amplification (LAMP) with a highly sensitive and label-free readout method called particle diffusometry for quantification of HIV viral load in a hand held platform with minimal process steps. Specific milestones include: 1) optimization of LAMP assays to ensure the lowest possible limit of detection, 2) optimization of a microfluidic test chip for minimal sample prep, 3) algorithm development and testing to obtain real-time viral detection. Assessment of usability and stakeholder needs with our partners at Moi University (Moi) in Eldoret, Kenya, and Indiana University School of Medicine (IUSM) in Indianapolis, Indiana will ensure that the handheld platform and HIV test will be readily adopted by stakeholders. At the conclusion of the R61 phase we will have a platform that is ready for implementation testing. The objective of the R33 phase is to develop a proof-of-concept device that is validated in small manufacturing runs and fully assessed against clinical performance metrics in plasma and whole blood. The handheld platform and test chips will be evaluated for process control reproducibility and an initial pilot clinical study will be performed with banked or prospectively collected samples from HIV patients at IUSM and Moy University. The outcome of this R33 Phase will be a highly characterized, sensitive, quantitative handheld HIV viral load detection platform that performs robustly with real clinical samples and is ready for scale up. Completion of these objectives will position us for FDA pre-submission and regulatory approval, rapid scale up, and implementation of a highly accurate HIV viral load self-test in the U.S. and East Africa. By enabling patients to monitor their HIV viral load while remaining connected to healthcare provider support, we will help to reduce barriers to treatment compliance and ultimately increase the number of patients with sustained viral load suppression as called for by the UNAIDS 90-90-90 targets.

摘要 摘要 联合国艾滋病规划署 (UNAIDS) 认可的 90-90-90 目标建议对全世界 90% 的艾滋病毒感染者进行诊断， 让 90% 的人接受有效的抗逆转录病毒治疗，并确保 90% 的治疗者实现 到 2020 年持续抑制病毒载量。遗憾的是，美国还没有做好实现这一目标的准备；仅有的 目前，美国 30% 的 HIV 感染者实现了病毒载量抑制。显然，范式转变 为了实现这一目标，需要进行病毒载量测试。该提案旨在创建一个定量的、手持式的、 病毒载量自检可供患者自己使用，以支持他们对这种慢性病的管理 状况并向远程医疗保健提供者提供相关的临床见解。 基于我们的前期工作，R61 阶段的目标是将等温循环结合起来 介导的核酸扩增（LAMP），具有高度灵敏且无标记的读出方法，称为 颗粒扩散测定法，用于在手持平台上以最少的处理步骤量化 HIV 病毒载量。 具体的里程碑包括：1) 优化 LAMP 检测以确保尽可能低的检测限，2) 优化微流体测试芯片以实现最少的样品制备，3) 算法开发和测试以获得 实时病毒检测。与莫伊大学的合作伙伴一起评估可用性和利益相关者的需求 肯尼亚埃尔多雷特的 (Moi) 和印第安纳州印第安纳波利斯的印第安纳大学医学院 (IUSM) 将确保 手持平台和艾滋病毒测试将很容易被利益相关者采用。 R61结束时 阶段我们将拥有一个准备好实施测试的平台。 R33 阶段的目标是开发一种概念验证设备，并在小型设备中进行验证。 生产运行并根据血浆和全血的临床性能指标进行全面评估。这 将评估手持平台和测试芯片的过程控制再现性和初步试点临床 研究将使用 IUSM 和 Moy 储存的或前瞻性收集的 HIV 患者样本进行 大学。 R33 阶段的成果将是高度表征、灵敏、定量的手持式 HIV 病毒载量检测平台可在真实临床样本中表现稳健，并已准备好扩大规模。 完成这些目标将使我们能够快速获得 FDA 的预提交和监管批准 扩大规模，并在美国和东非实施高度准确的艾滋病毒病毒载量自检。经过 使患者能够监测其 HIV 病毒载量，同时保持与医疗保健提供者支持的联系，我们 将有助于减少治疗依从性的障碍，并最终增加患有该病的患者数量 正如联合国艾滋病规划署 90-90-90 目标所要求的那样，持续抑制病毒载量。