Pont-of-use Acute HIV Infection Diagnostic for Substance Using Populations

针对药物使用人群的使用点急性 HIV 感染诊断

• 批准号: 10056083
• 负责人: Jacqueline Linnes
• 金额: $ 232.5万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10056083
• 关键词: Acquired Immunodeficiency Syndrome; Acute; Adopted; Adoption; Alcohol or Other Drugs use; Antigens; Blood; Blood specimen; Buffers; Caring; Chicago; Clinical; Community Health Aides; Continuity of Patient Care; Detection; Devices; Diagnosis; Diagnostic; Diagnostic tests; Drops; Drug user; Ensure; Face; Fingers; Foundations; Gap Junctions; Geography; Goals; HIV; HIV Infections; HIV diagnosis; Harm Reduction; Hepatitis C; Human immunodeficiency virus test; Individual; Infection; Intervention; Mediating; Needle-Exchange Programs; Nucleic Acids; Performance; Plasma; Population; Process; Public Health; Research; Sampling; Site; Substance Abuse Treatment Centers; Substance abuse problem; Technology; Testing; Time; Virus; Visual; Whole Blood; Work; barrier to care; base; clinically relevant; community based participatory research; health care availability; high risk; improved; novel strategies; prevent; social; substance abuse treatment; success; transmission process; usability; user-friendly; viron

SUMMARY Over 100 new HIV infections occur each day in the US, yet current rapid diagnostic tests (RDTs) that screen for HIV cannot detect acute HIV infections (AHIs) during the first weeks and months when newly infected individuals are the most likely to spread the virus to others. Further, people who use drugs (PWUD) are 22 times more likely to acquire HIV than the average population and face social, geographical, and institutional barriers that limit their access to HIV testing and care. To overcome this challenge at the nexus of substance abuse and HIV, there is an urgent need for a radically new approach to diagnose AHIs in order to engage PWUD in the care continuum at the earliest stages of infection and prevent transmission of HIV. Building on our preliminary work, we will combine current HIV p24-based RDTs detection strategies with isothermal loop-mediated nucleic acid amplification (LAMP) enabling highly sensitive detection of HIV. We will then integrate this into a robust and user-friendly handheld AHI testing platform. Targeting the highly abundant p24 antigen and leveraging this to initiate LAMP will improve sensitivity over RDTs by >2000x. This addition of an amplification control will provide clinically relevant differentiation of invalid tests from false negative tests. As with current RDTs, this entire process will require only 3 simple steps for the user: First, a drop of blood is added to the sample pad. Next, the user dispenses a buffer solution. After a brief waiting period, the user reads the visual yes/no result. The success of this, and all technology platforms will depend on adoption by, and delivery to, PWUD and others involved in their treatment. We will work with PWUD, community health workers, substance abuse treatment centers, harm reduction partners, and public health departments to perform community-based participatory research into the existing barriers to HIV testing and care faced by PWUD. Early assessment of device feasibility, acceptability, and usability by these same partners will ensure that the handheld AHI test will be readily adopted by stakeholders. In partnership with the Third Coast Center for AIDS Research in Chicago, we will evaluate our proof-of-concept device against clinical performance metrics in plasma and whole blood. The successful completion of this work will produce a user-approved field-ready AHI tests capable of detecting the equivalent of <1000 HIV virons/mL from a finger prick blood sample within 30 minutes. This new testing paradigm would transform the HIV care continuum by making critical AHI detection possible in the field, at sites ranging from substance abuse treatment facilities to syringe services programs. The platform developed in this work will lay the foundation for providing PWUD with targeted interventions that meet their needs and remove barriers to HIV care as well as additional diagnostics such as rapid Hepatitis C detection.

总结 在美国，每天都有超过100例新的艾滋病毒感染，但目前的快速诊断测试（RDTs） 艾滋病毒筛查不能在新感染的最初几周和几个月内检测出急性艾滋病毒感染（AHI）。 感染者最有可能将病毒传播给他人。吸毒者（PWUD） 感染艾滋病毒的可能性是平均人口的22倍， 体制障碍限制了她们获得艾滋病毒检测和护理的机会。为了克服这一挑战， 药物滥用和艾滋病毒，迫切需要一种全新的方法来诊断AHIs， 在感染艾滋病毒的最初阶段，让艾滋病毒/艾滋病感染者参与连续护理，并预防艾滋病毒的传播。 在我们前期工作的基础上，我们将联合收割机结合目前基于HIV p24的RDTs检测策略， 等温环介导的核酸扩增（LAMP）能够实现HIV的高灵敏度检测。我们将 然后将其集成到一个强大且用户友好的手持式AHI测试平台中。以高丰度的 p24抗原，并利用其启动LAMP将使RDT的灵敏度提高> 2000倍。的这种添加 扩增对照将提供无效测试与假阴性测试的临床相关区分。作为 使用当前的RDT，整个过程对用户来说只需要3个简单的步骤：首先， 添加到样品垫。接下来，用户分配缓冲溶液。经过一段短暂的等待，用户阅读 是/否的视觉结果。 这一平台以及所有技术平台的成功将取决于PWUD的采用和交付， 其他参与治疗的人。我们将与PWUD，社区卫生工作者，药物滥用， 治疗中心、减少伤害合作伙伴和公共卫生部门，以执行基于社区的 对艾滋病毒检测和艾滋病患者面临的现有障碍进行参与性研究。及早评估 这些合作伙伴的设备可行性、可接受性和可用性将确保手持式AHI测试 被利益相关者采纳。与芝加哥的第三海岸艾滋病研究中心合作， 我们将根据血浆和全血的临床性能指标评估我们的概念验证设备。 这项工作的成功完成将产生一个用户批准的现场准备AHI测试，能够 在30分钟内从手指穿刺血液样本中检测出相当于<1000 HIV病毒/mL的病毒。这个新 检测范式将通过使关键的AHI检测成为可能， 从药物滥用治疗设施到注射器服务项目。平台 在这项工作中开发的将为PWUD提供有针对性的干预措施奠定基础， 我们的目标是满足需求，消除艾滋病毒护理以及其他诊断（如丙型肝炎快速检测）的障碍。