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

基本信息

批准号：
10219917
负责人：
Giffin Daughtridge
金额：
$ 72.14万
依托单位：
URSURE, INC.
依托单位国家：
美国
项目类别：
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/10219917
关键词：
AIDS prevention Address Adherence Affinity Architecture 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 point of care testing pre-exposure prophylaxis prevent programs prototype resistant strain scale up seroconversion success tandem mass spectrometry test strip therapy adherence tool user-friendly validation studies

项目摘要

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范围内一种危险且普遍的疾病，导致数以百万计的感染者和每年死亡人数和数百亿美元的医疗费用。暴露前预防 (PrEP) 为 99% 如果每天服用，可以有效预防艾滋病毒感染，但其对减少艾滋病毒负担的影响因贫困而受到限制。坚持。疾病控制中心 (CDC) 建议对高危人群进行 PrEP HIV 感染，包括男男性行为者、静脉注射吸毒者和 HIV 感染者积极的伙伴。同样，用于治疗艾滋病毒的抗逆转录病毒疗法可以有效抑制病毒载量当遵循给药方案时。由于依从性差，不仅患者得不到适当的治疗，产生耐药菌株的机会增加。药物依从性监测众所周知可以改善药物合规性，但尚无用于快速长期监测 PrEP 和 ART 依从性的商业产品。因此，迫切需要一种工具来帮助医生监测 PrEP 的依从性和患者的 ART。为了患者可以接受并且在医生工作流程中可行，这种依从性测试需要微创、无痛、便宜、易于管理并提供快速、准确的结果。值得注意的是，现有的 SBIR 拨款正在资助 UrSure 开发 POC 测试，用于代谢物替诺福韦（TFV）。 TFV 测试衡量最近的依从性（最近一次服用剂量是什么时候）过去 7 天），而本申请建议开发一种测试来测量替诺福韦二磷酸盐这是长期依从性的衡量标准（过去 6 周内平均服药次数）。该项目的总体目标是开发一种即时检测 (POC) 测试，用于测量长期坚持 PrEP 和 ART。 POC 测试将基于测量细胞内的现有文献 TFV-DP 使用基于实验室的质谱分析法。 POC 检测会更快（几分钟即可得到结果）可在临床就诊期间用于衡量 PrEP 和 ART 的依从性，并在适当情况下为患者提供咨询关于如何提高他们的合规性。还有证据表明 TFV-DP 水平是病毒感染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疗效。该项目的目标是：1）优化和筛选前 3 个单克隆抗体抗体，3) 建立 LFIA 测试条的基本性能和架构，4) 优化性能 POC 设备并生产验证批次，以及 5) 放大化验程序，并生产试点批次以确保批次间的再现性。该直接进入第二阶段项目的最终成果将是具有高灵敏度/特异性的单克隆抗体，验证了横向流动免疫测定 TFV-DP 血液 POC 测试可长期坚持替诺福韦，以及 3 名试点批次以确保批次间的重现性。该项目的成功完成将使我们能够启动 FDA 验证研究并将我们的上市前 501k 汇总以供 FDA 批准。