An Aptamer-Based Biosensor for Point-of-Care Monitoring of Adherence to Oral Tenofovir Antiretroviral Regimens for HIV Prevention and Treatment

基于适体的生物传感器，用于即时监测艾滋病毒预防和治疗的口服替诺福韦抗逆转录病毒疗法的依从性

• 批准号: 9927250
• 负责人: Terry Ann Jacot
• 金额: $ 14.46万
• 依托单位: EASTERN VIRGINIA MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-18 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9927250
• 关键词: AIDS prevention; Adherence; Animals; Anti-Retroviral Agents; Antibodies; Antiviral resistance; Area; Bacteria; Base Pairing; Bedside Testings; Behavior; Binding; Biological; Biological Assay; Biosensor; Biotechnology; Blood; Buffers; Cell Culture Techniques; Clinic; Clinical; Clinical Research; Clinical Trials; Counseling; DNA; Data; Detection; Developing Countries; Development; Diagnosis; Dose; Drug Combinations; Drug Kinetics; Drug Monitoring; Effectiveness; Electric Conductivity; Electrodes; Epidemic; Equipment; Event; Feedback; Foundations; Fumarates; Gold; Growth; HIV; HIV Infections; HIV risk; HIV-1; Health Personnel; Hour; Human; Human Resources; Hybrids; Infection; Intervention; Laboratories; Life Style; Ligands; Liquid Chromatography; Liquid substance; Measures; Methylene blue; Monitor; Noise; Nucleic Acids; Oral; Oxidation-Reduction; Participant; Pharmaceutical Preparations; Pharmacotherapy; Plasma; Procedures; Production; RNA; Randomized; Regimen; Reporter; Reproducibility; Research; Research Activity; Risk; Sampling; Sexual Transmission; Ships; Signal Transduction; Specificity; Sulfhydryl Compounds; Swab; Technology; Tenofovir; Testing; Text Messaging; Time; Treatment Protocols; United Nations; Urine; Vagina; Visit; Woman; Youth; aptamer; base; dosage; emtricitabine; injection drug use; medication compliance; men; novel; pill; point of care; pre-exposure prophylaxis; preclinical development; prophylactic; real time monitoring; sensor; sex; small molecule; tandem mass spectrometry; therapeutic evaluation; tool; treatment adherence; truvada; vaginal fluid; young man; young woman

Project Summary According to UNAIDS, there were 36.9 million people around the world living with HIV and more than 1.8 million new infections that were diagnosed in 2017. The epidemic is not under control, and a significant growth of youth in developing countries will only compound the problem. Truvada®, a pill composed of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC), is the only drug approved for pre-exposure prophylaxis (PrEP) for men and wormen during high HIV risk activities. Adherence to the one pill per day regimen is crucial for significantly reducing potential HIV risk by sexual transmission. Therefore, monitoring drug levels in real time in the clinic would provide necessary interventions to support adherence, particularly during behavior or lifestyle changes. While pharmacokinetic approaches exist for measuring Truvada’s active drug metabolite, tenofovir (TFV), there is still no point-of-care test to measure TFV in HIV prevention or treatment regimens. Our project is aimed at filling this gap by developing and validating a novel aptamer-based biosensor, or aptasensor, capable of detecting tenofovir in various biological fluids, at the point-of-care/clinic, with a simple-to-use procedure, which will empower health care providers to provide real-time feedback with each prescription renewal. Aptamers are DNA or RNA-based ligands capable of binding specifically to small molecules. Because of their small size, stability, high specificity, and reproducibility, aptamers can be applied to biosensor platforms to create a compact and sensitive assay well-suited for point-of-care tests. Combining a technology generated by Base Pair and CONRAD’s expertise in the area of HIV prevention, we propose to develop and clinically validate an aptasensor for measuring TFV. In Specific Aim 1, the TFV- specific aptamer combined with a biosensor platform will be optimized and tested in TFV-spiked simulant and clinical samples. We will validate the apatasensor in a pilot clinical trial in women taking Truvada at high and low adherence treatment regimens in Specific Aim 2. This project will provide proof-of-concept for a TFV aptasensor that can be further validated as a point-of-care test for therapeutic drug and adherence monitoring. Ultimately, real-time monitoring of adherence will lead to better counselling, resulting in higher effectiveness, and greatly contribute to the global initiative to reduce new HIV infections to fewer than 500,000 by 2020.

项目摘要 据联合国艾滋病规划署称，全世界有3690万艾滋病毒感染者， 2017年确诊的新感染病例超过180万例。目前疫情尚未 发展中国家的青年人数大幅增长只会使问题更加复杂。 Truvada®是一种由富马酸替诺福韦酯（TDF）和恩曲他滨（FTC）组成的药丸， 唯一一种被批准用于男性和女性在艾滋病毒高感染率期间的暴露前预防（PrEP）的药物 风险活动。坚持每天一片的方案是至关重要的， 性传播的潜在艾滋病毒风险。因此，监测药物水平在真实的时间， 诊所将提供必要的干预措施，以支持依从性，特别是在行为或 生活方式的改变虽然存在药代动力学方法来测量特鲁瓦达的活性药物， 尽管代谢物替诺福韦（TFV）在HIV预防中的应用非常广泛，但仍然没有即时检测来测量TFV 或治疗方案。我们的项目旨在通过开发和验证一种新的 基于适体的生物传感器或适体传感器，能够检测各种生物样品中的替诺福韦， 液体，在护理点/诊所，使用简单的程序，这将使医疗保健 提供者提供每次处方更新的实时反馈。适体是DNA或 基于RNA的配体，能够特异性结合小分子。由于它们的体积小， 稳定性、高特异性和再现性，适体可应用于生物传感器平台， 创建一个紧凑和灵敏的分析非常适合现场护理测试。将一项技术 由Base Pair和CONRAD在艾滋病毒预防领域的专业知识产生，我们建议 开发并临床验证用于测量TFV的适体传感器。在具体目标1中，TFV 与生物传感器平台组合的特异性适体将被优化，并在TFV-掺入的细胞中进行测试。 模拟和临床样品。我们将在一项针对女性的试点临床试验中验证apatasensor 在Specific Aim 2中以高和低依从性治疗方案服用Truvada。该项目将 为TFV适体传感器提供概念验证，可作为床旁检测进一步验证 用于治疗药物和依从性监测。最终，对遵守情况的实时监控将 导致更好的咨询，从而提高效率，并大大有助于全球 到2020年将新的艾滋病毒感染人数减少到50万人以下。