A Point of Care Test to Monitor Long-Term Adherence to Tenofovir-based Regimens For The Prevention and Treatment of HIV

用于监测长期坚持以替诺福韦为基础的艾滋病毒预防和治疗方案的护理测试

• 批准号: 10010897
• 负责人: Giffin Daughtridge
• 金额: $ 75.71万
• 依托单位: URSURE, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-20 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10010897
• 关键词: AIDS prevention; Address; Adherence; Affinity; Architecture; Bedside Testings; Biological Assay; Blood; Blood Tests; Blood specimen; Centers for Disease Control and Prevention (U.S.); Cessation of life; Clinic Visits; Clinical; Contracts; Counseling; Dangerousness; Data; Development; Devices; Diagnostic tests; Diphosphates; Disease; Documentation; Dose; Ensure; Enzyme-Linked Immunosorbent Assay; Evaluation; Exposure to; Funding; Future; Generations; Goals; Grant; HIV; HIV Infections; HIV Seropositivity; Health; Health Benefit; Health Care Costs; Immunoassay; Individual; Industry Standard; Infection; International; Laboratories; Lateral; Liquid Chromatography; Literature; Manufacturer Name; Mass Spectrum Analysis; Measures; Monitor; Monoclonal Antibodies; Outcome; Painless; Patients; Performance; Pharmaceutical Preparations; Phase; Physicians; Population; Positioning Attribute; Prevention; Procedures; Production; Prophylactic treatment; Provider; Public Health; Quality Control; Regimen; Reproducibility; Research; Resources; Risk; Schedule; Sensitivity and Specificity; Small Business Innovation Research Grant; Specificity; Technology; Technology Transfer; Tenofovir; Test Result; Testing; Time; Treatment Protocols; Urine; Viral; Viral Load result; Viremia; Visit; Whole Blood; antiretroviral therapy; base; clinical efficacy; compliance behavior; cost; cross reactivity; high risk; immunogenic; improved; infection risk; insight; instrumentation; intravenous drug user; medication compliance; men who have sex with men; minimally invasive; novel; pilot lot production; point of care; pre-exposure prophylaxis; prevent; programs; prototype; resistant strain; scale up; seroconversion; success; tandem mass spectrometry; therapy adherence; tool; user-friendly; validation studies

PROJECT ABSTRACT HIV remains a dangerous and prevalent disease globally contributing to millions of infections and deaths per year and tens of billions of dollars in healthcare costs. Pre-Exposure Prophylaxis (PrEP) is 99% effective at preventing HIV infection if taken daily, but its impact on reducing HIV burden is limited by poor adherence. PrEP is recommended by the Centers for Disease Control (CDC) in populations at a high risk of HIV infection, which include men who have sex with men, intravenous drug users, and people with a HIV positive partner. Similarly, antiretroviral therapy, used to treat HIV, can be effective and suppress viral load when following the dosing schedule. Due to poor adherence, not only are patients inappropriately treated, the chance of developing resistant strains is increased. Drug adherence monitoring is well known to improve drug compliance, but there are no commercial products for rapid long-term adherence monitoring of PrEP and ART. Hence, there is a critical unmet need for a tool that will allow physicians to monitor adherence to PrEP and ART in patients. To be acceptable to patients and feasible in the physician workflow, this adherence test needs to be minimally-invasive, painless, inexpensive, easy to administer and provide rapid, accurate results. Of note, an existing SBIR grant is funding the development at UrSure of a POC test for the metabolite Tenofovir (TFV). The TFV test measures recent adherence (when was the most recent dose taken over the last 7 days) while this application proposes developing a test to measure Tenofovir Diphosphate which is a measure of long-term adherence (average number of doses taken over the last 6 weeks). The overall goal of this project is to develop a point-of-care (POC) test that will measure long-term adherence with PrEP and ART. The POC test will be based on existing literature that measures intracellular TFV-DP using a laboratory-based mass spectrometry. The POC assay will be faster (minutes to get a result) and can be used during a clinic visit to measure PrEP and ART adherence and, if appropriate, counsel patients on how to improve their compliance. There is also evidence that TFV-DP level is a reliable indicator of viral suppression, and prediction of future viremia or seroconversion, offering provider valuable information and improving clinical efficacy. The aims of this project are to: 1) optimize and screen for the top 3 monoclonal antibodies, 3) establish basic performance and architecture of an LFIA test strip, 4) optimize the performance of the POC device and produce a verification lot, and 5) Scale-up assay procedures, and produce pilot lots to ensure lot-to-lot reproducibility. The final deliverables of this Direct to Phase II project will be mAbs with high sensitivity/specificity, a validated Lateral Flow Immunoassay TFV-DP blood POC test for long-term tenofovir adherence, and 3 pilot lots to ensure lot-to-lot reproducibility. Successful completion of this project will leave us in a position to start FDA validation studies and put together our pre-market 501k for FDA approval.

项目摘要 艾滋病毒仍然是全球危险且普遍的疾病，导致数百万感染和 每年死亡和数百亿美元的医疗费用。暴露前预防（PREP）为99％ 有效防止每天感染艾滋病毒感染，但其对减轻艾滋病毒负担的影响受到贫困的限制 坚持。疾病控制中心（CDC）在人口中建议使用PREP 艾滋病毒感染，包括与男性发生性关系的男性，静脉吸毒者和艾滋病毒的患者 积极的伴侣。同样，用于治疗HIV的抗逆转录病毒疗法可以有效并抑制病毒载量 遵循给药时间表时。由于依从性差，不仅患者不恰当地治疗 增加抗性菌株的机会增加了。众所周知，药物依从性监测可以改善药物 合规性，但没有用于快速长期依从性预备和艺术的商业产品。 因此，对于一种工具，至关重要的需要，该工具将允许医生监视依从性进行准备 和患者的艺术。为了被患者接受并在医师工作流程中可行，这种依从性 测试需要微创，无痛，廉价，易于管理，并提供快速，可提供 准确的结果。值得注意的是，现有的SBIR赠款正在为POC测试的开发提供资金 代谢物替诺福韦（TFV）。 TFV测试措施最近依从性（最新剂量是什么时候 在过去的7天中）虽然该应用程序提出了一项测试以测量双磷酸盐的测试 这是长期依从性的量度（在过去6周内服用的平均剂量数量）。 该项目的总体目标是开发一个护理点（POC）测试，该测试将衡量长期 遵守准备和艺术。 POC测试将基于测量细胞内的现有文献 使用基于实验室的质谱法进行TFV-DP。 POC分析将更快（分钟以获得结果） 并且可以在诊所访问期间使用以衡量准备和艺术依从性，并在适当的情况下咨询患者 关于如何提高其合规性。也有证据表明TFV-DP水平是病毒的可靠指标 抑制和预测未来的病毒血症或血清转化，为提供者提供有价值的信息和 提高临床功效。该项目的目的是：1）优化和筛选前3个单克隆 抗体，3）建立LFIA测试条的基本性能和架构，4）优化性能 POC设备并生成验证批次，以及5）扩展测定程序，并生产飞行员批次 确保重复可重复性。 该直接到II期项目的最终可交付成果将是具有高灵敏度/特异性的mAB，一个 经过验证的横向流量免疫测定TFV-DP血液POC测试长期替诺福韦依从性和3个飞行员 大量可确保大量重现性。成功完成该项目将使我们处于 开始FDA验证研究，并将我们的预赛前501K汇总为FDA批准。