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

项目摘要 该阶段II SBIR项目的目标是开发一种即时（POC）测试，以测量患者 坚持暴露前预防（PrEP）作为预防艾滋病毒感染的措施 已知有感染艾滋病毒的风险。艾滋病毒每年造成数百万人感染和死亡， 数十亿美元的医疗费用。PrEP是由疾病中心推荐的 控制和世界卫生组织在高危人群中的艾滋病毒暴露。99%的预防效果 如果每天服用，艾滋病毒感染，但其对减少艾滋病毒负担的影响因依从性差而受到限制。监测 患者的实际药物使用可以提高药物依从性，但没有PrEP的商业测试。 UrSure快速TFV POC测试将根据UrSure实验室质量测量PrEP依从性 替诺福韦（TFV）的光谱尿液测试，这是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。它可以在门诊期间使用 访问以衡量PrEP依从性，并在适当的情况下，就如何提高依从性向患者提供咨询。以来 Truvada是确认HIV感染的常见一线治疗，该测试还将测量患者的依从性。 已知的艾滋病毒阳性患者无法获得频繁的病毒载量检测。 该项目的第一阶段证明了这一方法的可行性。合成了一种新的TFV衍生物 并用于产生对TFV特异和敏感的多克隆抗体。ELISA原型是 开发并验证了尿液样本确认为阳性或阴性的TFV，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， 商业化目的是：1）产生多达三种具有灵敏度的单克隆抗体， 对尿液中TFV特异性>95%; 2）使用这些单克隆抗体开发侧流免疫测定 （LFIA）条; 3）将该条与自含式测定盒集成并优化其性能; 4）验证 LFIA的性能，并准备制造; 5）将LFIA原型转移到合同中 生产商并生产验证批次。UrSure与LFIA专家建立了良好的关系， 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II期项目的最终可交付成果将是对TFV敏感和特异的单克隆抗体， 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灵敏度和特异性至少为85%的检测。成功 该第二阶段项目的完成将产生一个适合启动FDA监管的原型， 过程预计将进行2类重新分类，并将支持POC检测的商业化。

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.