A Rapid Point-of-Care Test to Improve ART and PrEP Adherence

项目总结/摘要 口服抗逆转录病毒疗法（ART）对艾滋病毒感染者预防传播和艾滋病毒感染非常有效。 未感染的人，以防止收购，称为暴露前预防（PrEP），但监测和 改善药物依从性一直是具有挑战性的。世界卫生组织建议所有艾滋病毒感染者 所有有感染艾滋病毒重大风险的人都接受PrEP，优先考虑高发病率 在美国和发展中国家，两组（≥3例感染/100人-年）。然而，ART和PrEP 只有当人们维持相当于每周≥4次剂量的药物水平时才有效。许多患者接受ART治疗 或PrEP难以坚持，临床医生目前没有可用的工具来监测药物水平， 坚持提供有针对性的咨询和支持。我们提出了一种简单、快速、即时的检测方法， 监测ART或PrEP药物依从性可能是临床医生和患者监测药物水平的有用工具， 指导坚持咨询，这可能会导致减少艾滋病毒传播和更好地协调艾滋病毒预防 努力自2013年以来，我们一直在开发一种简单的即时检测方法， 测量替诺福韦，ART和PrEP的主要药物。2016年，我们启动了NIH资助的药代动力学研究， 研究，以建立必要的检测限和药物水平，为我们的床旁护理PrEP依从性测试。 因此，我们将完成替诺福韦快速检测的开发，将技术转移到横向流 具有适当检测阈值的床旁检测格式，并进行临床可行性、可接受性 和验证研究在当地的PrEP诊所。我们在此应用程序中的目标是完成一个 快速侧流护理点测试，以监测和改善对ART和PrEP的依从性，并评估可行性， 可接受性，并在PrEP诊所进行验证。我们计划通过以下方式来检验我们的中心假设 三个具体目标：（1）优化缓冲液、血液和尿液中替诺福韦的检测和测量 使用抗体、适体或纳米抗体的免疫测定样品;（2）为了将免疫测定组分转移到免疫测定样品中， 侧流分析格式，并建立血液和尿液中替诺福韦的定量范围和检测限 （3）评估替诺福韦即时检测在PrEP中的临床可行性和有效性 临床环境中的供应商和患者。这项工作是创新的，因为它开发了一个全新的类别 用于监测依从性的快速诊断测试，这将有助于患者和临床医生改善ART和PrEP 坚持和预防艾滋病毒传播。在这个项目的最后，我们希望有一个快速的侧流测定 这将适用于未来的大规模临床实施试验。如果我们的快速替诺福韦坚持测试 被证明是有价值的和具有成本效益的，那么它可以很容易地在世界各地的诊所实施，包括 资源有限的环境。

PROJECT SUMMARY/ABSTRACT Oral antiretroviral therapy (ART) is highly effective for HIV-infected people to prevent transmission and HIV- uninfected people to prevent acquisition, known as pre-exposure prophylaxis (PrEP), but monitoring and improving drug adherence have been challenging. The World Health Organization recommends all HIV-infected people receive ART and all people at substantial risk of HIV infection receive PrEP with priority for high incidence groups (≥3 infections/100 person-years) in both the US and developing countries. However, ART and PrEP are only effective when people maintain drug levels equivalent to ≥4 doses per week. As many patients taking ART or PrEP have difficulty with adherence, clinicians currently have no available tools to monitor drug levels or adherence to provide targeted counseling and support. We propose that a simple, rapid, point-of-care assay to monitor ART or PrEP drug adherence could be a useful tool for clinicians and patients to monitor drug levels and guide adherence counseling, which may lead to less HIV transmission and better coordination of HIV prevention efforts. Since 2013, we have been developing a simple, point-of-care assay to accurately and inexpensively measure tenofovir, the primary drug of both ART and PrEP. In 2016, we initiated an NIH-funded pharmacokinetic study to establish the necessary limit of detection and drug levels for our point-of-care PrEP adherence test. Therefore, we will complete the development of the rapid tenofovir test, transfer the technology to a lateral flow point-of-care assay format with the appropriate detection threshold, and conduct a clinical feasibility, acceptability and validation study in a local PrEP clinic. Our objective in this application is to complete the development of a rapid lateral flow point-of-care test to monitor and improve adherence to ART and PrEP, and to assess feasibility, acceptability, and validation in a PrEP clinic. We plan to test our central hypotheses by pursuing the following three specific aims: (1) To optimize the detection and measurement of tenofovir in buffer, blood, and urine specimens using antibodies, aptamers, or nanobodies; (2) To transfer the immunoassay components into a lateral flow assay format and establish the quantitative range and limit of detection of tenofovir in blood and urine specimens; (3) To assess clinical feasibility and validation of the point-of-care tenofovir test among PrEP providers and patients in a clinical setting. This work is innovative because it develops an entirely new category of rapid diagnostic test for monitoring adherence, which will help patients and clinicians improve ART and PrEP adherence and prevent HIV transmission. At the end of this project, we expect to have a rapid lateral flow assay that will be suitable for a future large-scale clinical implementation trial. If our rapid tenofovir adherence test proves to be valuable and cost-effective, then it could be easily implemented in clinics worldwide, including resource-limited settings.