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

摘要 在美国，每天都有超过100例新的艾滋病毒感染病例，然而目前的快速诊断测试(RDT) 艾滋病毒筛查不能在最初的几周和几个月内检测到急性艾滋病毒感染(AHI) 受感染的人最有可能将病毒传播给其他人。此外，吸毒者(PWUD) 感染艾滋病毒的可能性是普通人群的22倍，并面临着社会、地理和 限制他们获得艾滋病毒检测和护理的体制障碍。为了克服这一挑战，在 药物滥用和艾滋病毒，迫切需要一种全新的方法来诊断AHIS，以便 在感染的最早阶段让PWUD参与护理连续体，防止艾滋病毒传播。 在前期工作的基础上，我们将把目前基于HIV p24的RDTs检测策略与 等温环介导的核酸扩增(LAMP)能够实现对艾滋病毒的高灵敏检测。我们会 然后将其集成到一个强大且用户友好的手持AHI测试平台中。目标是高度丰富的 P24抗原，并利用这一点来启动LAMP将提高敏感性比RDT；2000x。这项新增的 扩增对照将在临床上区分无效试验和假阴性试验。AS 使用目前的RDT，整个过程对于用户来说只需要3个简单的步骤：首先，一滴血 添加到样本板上。接下来，用户分配缓冲液。在短暂的等待期之后，用户会阅读 视觉上的是/否结果。 这项技术以及所有技术平台的成功将取决于PWUD和 其他参与他们治疗的人。我们将与PWUD、社区卫生工作者、药物滥用 治疗中心、减少危害合作伙伴和公共卫生部门以社区为基础执行 参与研究残障人士在艾滋病毒检测和护理方面面临的现有障碍。早期评估 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AHI测试将 很容易被利益相关者采纳。与芝加哥的第三海岸艾滋病研究中心合作， 我们将对照血浆和全血的临床性能指标来评估我们的概念验证设备。 这项工作的成功完成将产生用户批准的现场就绪AHI测试，能够 在30分钟内从手指刺血样本中检测出相当于1000个艾滋病毒/毫升的病毒。这是一项新的 检测范式将通过在现场实现关键的AHI检测来改变艾滋病毒护理的连续体， 从药物滥用治疗设施到注射器服务项目，不一而足。站台 这项工作将为为PWUD提供符合其要求的有针对性的干预奠定基础 需要并消除艾滋病毒护理的障碍，以及其他诊断，如丙型肝炎快速检测。

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.