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 遵守抗逆转录疗法（ART）和暴露前预防（PREP）对成功至关重要 HIV治疗和预防治疗。 遵守艺术或准备性。 艾滋病毒感染（来自失败的准备和倡导艺术），更多的耐药病毒（通过失败的艺术选择）， 并不必要切换到昂贵的第二或第三线艺术 但是，不遵守的不遵守）是为了解决这一关键知识差距 新型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 在全球范围内，指纹血液或尿液作为艺术和依从性的客观衡量 我们申请的目的是进行重要的下一步工作，以咨询这一点的测试：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测定法 研究健康的受控药物依从性并进行我们的飞行员验证研究 来自现有生物座的现实世界临床样本的新型护理测定法 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 客观的依从性衡量标准，我们的护理替诺福韦分析将有能力取消危害 不同的药物依从性水平。 目的：（1）评估我们在全血和尿液标本中的新型保健替诺福韦（TFV）测定 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， 适度，完美的依从性； 和尿液的标本使用现实世界中的临床HIV中的生物疗法预防。 是创新元素，因为它开发了一个全新的类别，用于监测艺术和 在临床医疗点上的依从性。 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 - 抗性病毒和不必要的艺术方案转换 - 措施改善了国家艾滋病毒计划 并有助于保留有效的蜂巢药物的全球供应。