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

• 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
• 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

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阶段SBIR项目的目标是开发一个护理点（POC）测试以测量患者 遵守暴露前预防（PREP）作为对艾滋病毒感染的预防 已知有艾滋病毒暴露的风险。艾滋病毒每年造成数百万的感染和死亡和数十 全球数十亿美元的医疗保健费用。疾病中心建议准备准备 控制和世界卫生组织的艾滋病毒风险高风险的人。它有效地预防99％ 艾滋病毒感染如果每天感染，但其对减轻艾滋病毒负担的影响受到依从性不佳的限制。监视 患者的实际使用药物可以改善药物依从性，但没有商业测试进行PREP。 URSURE快速TFV POC测试将根据基于URSURE实验室的质量测量依从性 Tenofovir（TFV）的光谱尿测试，这是PREP和TRUVADA的组成部分。 POC测试将 保持无创，毫无痛苦，快速（以获得结果的几分钟）且价格便宜。它可以在诊所中使用 访问以衡量预备依从性，并在适当的情况下咨询患者如何提高合规性。自从 Truvada是一种常见的一线疗法，用于确认的HIV感染，该测试还将测量 已知的HIV阳性患者无法获得频繁的病毒负荷测试。 该项目的第一阶段证明了这种方法的可行性。合成了一种新型的TFV衍生物 并用于产生对TFV的特异性和敏感的多克隆抗体。原型Elisa是 用尿液样品开发和验证TFV的尿液样本，用于评估 POC测试。建立了具有已知TFV结果的尿液样品库。 该阶段项目的目的是将URSURE TFV POC测试的开发推向 商业化。目的是：1）具有灵敏度和 尿液中TFV的特异性> 95％； 2）使用那些单克隆抗体开发侧向流免疫测定 （lfia）带; 3）将该条带与独立的测定盒进行整合，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 制造商和生产验证批次。 Ursure与LFIA专家建立了关系 在LFIA测定开发，验证和测定套件生产方面具有丰富经验的组织。 该阶段项目的最终可交付成果将是敏感的单克隆抗体，对TFV的特定于TFV 尿液，LFIA的锁定原型，用于快速检测尿液中的TFV，很多1,000个URSURE TFV POC 对TFV的尿液样品的敏感性至少为85％的测试。成功的 该阶段项目的完成将导致适合启动FDA调节的原型 过程。预计将进行2类新分类，并将支持POC测试的商业化。