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Unaids称，世界各地有3690万人患艾滋病毒， 2017年被诊断出的超过180万新感染。流行病不在 控制国家的控制和青年的显着增长只会加剧问题。 Truvada®是一种由替诺福韦毒毒素（TDF）和Emtricitabine（FTC）组成的药丸，是 仅在高艾滋病毒期间批准用于男性和蠕虫的预防前预防药物（PREP） 风险活动。遵守每天一丸对于显着降低至关重要 性传播潜在的艾滋病毒风险。因此，实时监测药物水平 诊所将提供必要的干预措施来支持依从性，特别是在行为或 生活方式改变。尽管存在用于测量Truvada活跃药物的药代动力学方法 代谢物，替诺福韦（TFV），仍未进行预防HIV预防TFV的护理测试 或治疗方案。我们的项目旨在通过制定和验证小说来填补这一空白 基于apatamer的生物传感器或Aptasensor，能够在各种生物学中检测Tenofovir 流体，在护理/诊所，采用简单使用程序，这将赋予医疗保健能力 提供者提供每个处方续订的实时反馈。伴侣是DNA或 基于RNA的配体能够特异性与小分子结合。由于它们的尺寸很小， 稳定性，高特异性和可重复性，适体可以应用于生物传感器平台 创建一个非常适合护理点测试的紧凑和敏感测定法。结合技术 由基础对和康拉德在预防艾滋病毒领域的专业知识产生，我们建议 开发和临床验证用于测量TFV的适率。在特定的目标1中，TFV- 特定的APATMER与生物传感器平台结合使用，将在TFV尖峰中进行优化和测试 模拟和临床样品。我们将在女性试验临床试验中验证Apatasensor 在特定目标2中以高和低依从性治疗方案进行Truvada。该项目将 为TFV Aptasensor提供概念验证，可以进一步验证作为护理点测试 用于治疗药物和依从性监测。最终，对依从性的实时监控将 导致更好的反销，从而提高效率，并为全球做出巨大贡献 到2020年，将新的艾滋病毒感染降低到不到500,000的倡议。