A Point of Care Test to Monitor and Promote Adherence to PrEP for HIV Prevention

用于监测和促进遵守 PrEP 预防 HIV 的护理点测试

基本信息

批准号：
9892581
负责人：
Giffin Daughtridge
金额：
$ 15.15万
依托单位：
URSURE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-01 至 2020-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9892581
关键词：
AIDS prevention AIDS/HIV problem Adherence Advanced Development Affinity Antibodies Architecture B-Lymphocytes Bedside Testings Biological Assay Blood Centers for Disease Control and Prevention (U.S.)Cessation of life Classification Clinic Clinic Visits Clinical Contracts Counseling Custom Dangerousness Development Devices Disease Documentation Dose Drug Combinations Drug Monitoring Drug usage Enzyme-Linked Immunosorbent Assay Epidemic Equipment Evaluation Future Goals HIV HIV Infections HIV Seropositivity Health Care Costs Hour Immunoassay Individual Industry Standard Infection Institutes Interruption Laboratories Lateral Liquid Chromatography Manufacturer Name Mass Spectrum Analysis Measures Medical Device Methods Monitor Monoclonal Antibodies Oryctolagus cuniculus Painless Patients Performance Persons Pharmaceutical Preparations Phase Prevention Procedures Process Production Quality Control Regimen Reporting Research Resources Risk Sampling Sensitivity and Specificity Sexually Transmitted Diseases Small Business Innovation Research Grant Specificity Specimen Handling Tenofovir Test Result Testing Urine Validation Viral Load result Work World Health Organization assay development base clinical application commercialization compliance behavior cross reactivity experience high risk improved infection risk innovation intravenous drug user medication compliance novel point of care polyclonal antibody pre-exposure prophylaxis prevent programs prototype rapid detection success tandem mass spectrometry truvada

项目摘要

PROJECT ABSTRACT The goal of this Phase II SBIR project is to develop a point-of-care (POC) test to measure patient adherence with Pre-exposure Prophylaxis (PrEP) as a prevention against HIV infection in people known to be at risk of HIV exposure. HIV contributes to millions of infections and deaths per year and tens of billions of dollars in healthcare costs around the world. PrEP is recommended by the Centers for Disease Control and World Health Organization in people at high risk for HIV exposure. It is 99% effective at preventing HIV infection if taken daily, but its impact on reducing HIV burden is limited by poor adherence. Monitoring actual drug use by patients improves drug adherence, but there is no commercial test for PrEP. The UrSure rapid TFV POC test will measure PrEP adherence based on the UrSure laboratory-based mass spectrometry urine test for tenofovir (TFV), which is a component of both PrEP and Truvada. The POC test will be noninvasive, painless, rapid (minutes to get a result) and inexpensive. It can be used during a clinic visit to measure PrEP adherence and, if appropriate, counsel patients on how to improve compliance. Since Truvada is a common first-line therapy for confirmed HIV infection, this test also will measure adherence in known HIV-positive patients who do not have access to frequent viral load testing. Phase I of this project demonstrated the feasibility of this approach. A novel TFV derivative was synthesized and used to produce polyclonal antibodies that are specific and sensitive for TFV. A prototype ELISA was developed and validated with urine samples confirmed as positive or negative for TFV, for use in evaluating the POC test. A urine sample bank with known TFV results was established. The objective of this Phase II project is to advance development of the UrSure TFV POC test toward commercialization. The Aims are to: 1) produce up to three monoclonal antibodies with sensitivity and specificity >95% for TFV in urine; 2) use those monoclonal antibodies to develop a Lateral Flow Immunoassay (LFIA) strip; 3) integrate that strip with a self-contained assay cassette and optimize its performance; 4) verify the performance of the LFIA and prepare it for manufacture; and 5) transfer the LFIA prototype to a contract manufacturer and produce validation lots. UrSure has relationships in place with LFIA experts and organizations with deep experience in LFIA assay development, validation and assay kit production. The final deliverables of this Phase II project will be monoclonal antibodies sensitive and specific for TFV in urine, a locked prototype of a LFIA for rapid detection of TFV in urine, and a lot of 1,000 UrSure TFV POC tests with at least 85% sensitivity and specificity for urine samples positive and negative for TFV. Successful completion of this Phase II project will result in a prototype suitable for initiating the FDA regulatory process. A Class 2 de novo classification is expected and will support commercialization of the POC test.

项目摘要该 II 期 SBIR 项目的目标是开发一种即时护理 (POC) 测试来测量患者的坚持暴露前预防 (PrEP) 作为预防人类艾滋病毒感染的措施已知有感染艾滋病毒的风险。艾滋病毒每年导致数百万人感染和死亡，并导致数十人死亡全球医疗保健费用达数十亿美元。 PrEP 是由疾病中心推荐的控制和世界卫生组织对艾滋病毒暴露高危人群的控制。预防有效率达 99% 如果每天服用，则会感染艾滋病毒，但其对减少艾滋病毒负担的影响因依从性差而受到限制。监控患者的实际用药可提高药物依从性，但 PrEP 尚无商业测试。 UrSure 快速 TFV POC 测试将根据 UrSure 实验室质量来测量 PrEP 依从性替诺福韦 (TFV) 的光谱尿液检测，它是 PrEP 和 Truvada 的组成部分。 POC 测试将无创、无痛、快速（几分钟即可获得结果）且价格低廉。可以在诊所期间使用拜访以衡量 PrEP 依从性，并在适当情况下建议患者如何提高依从性。自从 Truvada 是治疗确诊 HIV 感染的常见一线疗法，该测试还将衡量患者的依从性已知的艾滋病毒阳性患者无法进行频繁的病毒载量检测。该项目的第一阶段证明了该方法的可行性。合成了一种新型 TFV 衍生物并用于生产对 TFV 具有特异性和敏感性的多克隆抗体。 ELISA 原型是使用确认为 TFV 阳性或阴性的尿液样本进行开发和验证，用于评估 POC 测试。建立了具有已知 TFV 结果的尿液样本库。该第二阶段项目的目标是推进 UrSure TFV POC 测试的开发，以实现商业化。目标是：1) 生产多达三种具有敏感性和稳定性的单克隆抗体尿液中 TFV 的特异性 >95%； 2) 使用这些单克隆抗体开发侧流免疫分析 (LFIA) 条带； 3) 将该条带与独立的检测盒集成并优化其性能； 4）验证 LFIA 的性能并为制造做好准备； 5) 将 LFIA 原型转移到合同中制造商并生产验证批次。 UrSure 与 LFIA 专家建立了联系，并且在 LFIA 检测开发、验证和检测试剂盒生产方面拥有丰富经验的组织。该二期项目的最终成果将是对 TFV 敏感且特异的单克隆抗体尿液、用于快速检测尿液中 TFV 的 LFIA 锁定原型以及大量 1,000 UrSure TFV POC 对 TFV 阳性和阴性尿液样本的检测灵敏度和特异性至少为 85%。成功的该第二阶段项目的完成将产生适合启动 FDA 监管的原型过程。预计将进行 2 级重新分类，并将支持 POC 测试的商业化。