A Point-of-Care Assay to Measure Tenofovir for Monitoring PrEP and ART Adherence

用于监测 PrEP 和 ART 依从性的替诺福韦即时检测

• 批准号: 9312764
• 负责人: Paul K Drain
• 金额: $ 20.29万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-08 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9312764
• 关键词: AIDS prevention; Acquired Immunodeficiency Syndrome; Address; Adherence; Adult; Advanced Development; Bedside Testings; Biological Assay; Biomedical Engineering; Blood; Boston; Categories; Clinic; Clinical; Collaborations; Counseling; Detection; Development; Diagnostic tests; Drug Controls; Drug Kinetics; Fumarates; Future; Goals; HIV; HIV Infections; HIV prevention trial; Integrase Inhibitors; Knowledge; Lamivudine; Lateral; Measurement; Measures; Monitor; Participant; Patients; Performance; Pharmaceutical Preparations; Pharmacology; Prevention; Regimen; Research Infrastructure; Resources; Sampling; Site; Specimen; Tenofovir; Testing; Thailand; Therapeutic; Time; Urine; Whole Blood; Work; antiretroviral therapy; assay development; biobank; cost; drug resistant virus; experience; healthy volunteer; implementation trial; improved; innovation; liquid chromatography mass spectrometry; medication compliance; mortality; novel; point of care; pre-exposure prophylaxis; prevent; programs; scale up; success; therapy adherence; tool; transmission process; validation studies; virology

ABSTRACT Adherence to antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) are critical to the success of HIV treatment and therapeutic prevention. No accurate, objective point-of-care test is available to monitor adherence to either ART or PrEP. The inability to accurately identify poorly adherent patients will lead to more HIV infections (from failed PrEP and non-suppressive ART), more drug-resistant virus (selected by failing ART), and unnecessary switching to costly second- or third-line ART (when first-line regimens with virologic efficacy but non-adherence are stopped inappropriately). To address this critical knowledge gap, we have developed a novel point-of-care test to detect the presence of tenofovir—the most common drug in both ART and PrEP treatments worldwide—in fingerprick blood or urine as an objective measure of ART and PrEP adherence. The objective of our application is to conduct essential next-step work to advance this point-of-care test: we will assess our novel point-of-care assay in whole blood and urine specimens within a controlled pharmacokinetic study of healthy volunteers maintaining controlled drug adherence and conduct a pilot validation study of our novel point-of-care assay on real-world clinical samples from an existing biorepository. Our central hypothesis is that the pharmacokinetics of tenofovir in blood and urine will support point-of-care tenofovir detection as an objective measure of adherence, and that our point-of-care tenofovir assay will have the ability to discriminate different drug adherence levels. We will test our central hypotheses by pursuing the following two specific aims: (1) To assess our novel point-of-care tenofovir (TFV) assay in whole blood and urine specimens within a controlled pharmacokinetic study of HIV-negative adults receiving tenofovir disoproxil fumarate (TDF) with low, moderate, and perfect adherence; and (2) To validate our novel point-of-care tenofovir (TFV) assay on blood and urine specimens using an existing biorepository from a real-world clinical HIV prevention study. This work is innovative because it develops an entirely new category of rapid diagnostic testing for monitoring ART and PrEP adherence at the clinical point of care. Our rapid assay will help clinicians identify patients in need of more adherence counseling, which when implemented will prevent HIV acquisition, emergence of drug- resistant virus, and unnecessary ART regimen switching—measures that will improve national HIV programs and help preserve the global supply of an effective HIV medication.

抽象的 遵守抗逆转录病毒疗法（ART）和暴露前预防（PREP）对于成功的成功至关重要 HIV治疗和预防治疗。没有准确，客观的护理测试可以监视 遵守艺术或准备。无法准确识别依附的患者的准确识别会导致更多 艾滋病毒感染（来自失败的预备和非抑制艺术），更多的耐药病毒（通过失败的艺术选择）， 并不必要地转换为昂贵的二线或三线艺术（当具有病毒效率的一线方案时 但是，不遵守不适当）。为了解决这个关键的知识差距，我们已经建立了一个 新的护理测试以检测替诺福韦的存在，替诺福韦是艺术和准备中最常见的药物 全世界的治疗方法 - 用指纹血液或尿液作为艺术和预科依从性的客观衡量。这 我们应用的目的是进行基本的下一步工作，以推进这一保健测试：我们将 评估我们在受控药代动力学中的全血和尿液标本中的新型护理评估 对维持受控药物依从性的健康志愿者的研究并进行了对我们的试点验证研究 对现有生物座的现实世界临床样品的新型护理测定法。我们的中心假设 是血液和尿液中Tenofovir的药代动力学将支持替诺福韦的替诺福韦的检测 依从性的客观测量，并且我们的护理替诺福韦测定法将有能力歧视 不同的药物依从性水平。我们将通过追求以下两个具体的两个特定的假设来检验我们的中心假设 目的：（1）评估我们在全血和尿液标本中评估新颖的替诺福韦（TFV）评估 接受替诺福韦毒毒素富马酸（TDF）的HIV阴性成年人的对照药代动力学研究， 中等，完美的依从性； （2）验证我们对血液的新型护理替诺福韦（TFV）测定 和尿液标本，使用现实世界中的临床HIV预防研究中的现有生物座位。这项工作 具有创新性，因为它为监测艺术和 在临床护理点的准备依从性。我们的快速测定将帮助临床医生确定需要的患者 更多的依从性咨询，该咨询将在实施后阻止艾滋病毒收购，毒品的出现 - 抵抗病毒和不必要的艺术方案转换 - 可以改善国家艾滋病毒计划的方法 并帮助保留有效的HIV药物的全球供应。