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: 9345634
• 负责人: Giffin Daughtridge
• 金额: $ 22.02万
• 依托单位: URSURE, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-09 至 2018-06-08
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9345634
• 关键词: AIDS prevention; AIDS/HIV problem; Adherence; Affinity; Antibodies; Antibody Formation; Antigens; Bedside Testings; Biological Assay; Blood; Centers for Disease Control and Prevention (U.S.); Cessation of life; Chemicals; Clinic; Clinic Visits; Clinical; Counseling; Dangerousness; Devices; Disease; Dose; Drug Combinations; Drug Monitoring; Eligibility Determination; Enzyme-Linked Immunosorbent Assay; Epidemic; Equipment; Future; Goals; HIV; HIV Infections; HIV Seropositivity; Hair; Health Care Costs; Hour; Immunoassay; Individual; Infection; Interruption; Laboratories; Lateral; Liquid Chromatography; Mass Spectrum Analysis; Measures; Methods; Monitor; Monoclonal Antibodies; Painless; Patients; Persons; Pharmaceutical Preparations; Phase; Physicians; Population; Proteins; Recording of previous events; Regimen; Research; Resources; Risk; Sampling; Sensitivity and Specificity; Sexually Transmitted Diseases; Small Business Innovation Research Grant; Specimen Handling; Tenofovir; Test Result; Testing; Urine; Work; assay development; base; compliance behavior; design; high risk; immunogenic; improved; innovation; intravenous drug user; medication compliance; men who have sex with men; novel; point of care; polyclonal antibody; pre-exposure prophylaxis; prevent; programs; prototype; success; tandem mass spectrometry; tool; truvada

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. The use of Truvada as 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 known to have a high risk of HIV infection, which include men who have sex with men, people with a history of an STI, intravenous drug users, and people with a partner who is HIV positive. Monitoring of drug adherence is well known to improve drug compliance, but there are no commercial products for adherence monitoring of PrEP. Hence, there is a critical unmet need for a tool that will allow physicians to monitor adherence to PrEP in their patients. In order to be acceptable to patients on a routine basis and feasible in the physician workflow, this adherence test needs to be noninvasive, painless, inexpensive, and provide rapid, accurate results. The overall goal of this project is to develop a point-of-care (POC) test that will measure patient adherence with the PrEP regimen and ultimately prevent HIV infection in people known to be at risk of exposure. The POC test will be based on a laboratory-based mass spectrometry urine test for levels of tenofovir, one of the drugs in PrEP, which UrSure already developed. The POC assay will be faster (minutes to get a result) and therefore can be used during a clinic visit to measure PrEP adherence and, if appropriate, counsel patients on how to improve their compliance. The aims of this Phase I project are to: 1) synthesize four tenofovir derivatives and conjugate them to form two immunogens for polyclonal antibody production in Aim 2 and two HRP-conjugated proteins for ELISA use in Aim 3; 2) produce two affinity purified polyclonal antibodies against each of the two immunogens produced in Aim 1; and 3) develop a prototype ELISA using these derivatives and antibodies, which will be validated with urine samples positive and negative for tenofovir. The final deliverables of this Phase I project will be conjugated tenofovir derivatives, polyclonal antibodies to these derivatives, and an ELISA, all of which will be used to develop monoclonal antibodies and ultimately a Lateral Flow Immunoassay POC urine tenofovir test in a subsequent Phase II application. This Phase I project will be a critical step towards developing our POC urine test and bringing a powerful tool with the ability to drive PrEP adherence and reduce HIV infections to physicians worldwide.

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。使用 Truvada 作为预曝光 如果每天服用，预防 (PrEP) 可以有效预防 HIV 感染，但其对减少 HIV 感染的影响为 99% 负担因依从性差而受到限制。 PrEP 是美国疾病控制中心 (CDC) 推荐的 已知感染艾滋病毒的高风险人群，其中包括男男性行为者、患有艾滋病毒的人 有性传播感染病史、静脉注射吸毒者以及伴侣艾滋病毒呈阳性的人。药物监测 众所周知，坚持治疗可以提高药物依从性，但目前还没有用于坚持治疗的商业产品 PrEP 的监测。因此，对于一种允许医生监测的工具的迫切需求尚未得到满足。 患者坚持 PrEP 的情况。为了常规地为患者所接受并且在实践中可行 根据医生的工作流程，这种依从性测试需要是无创、无痛、廉价的，并提供 快速、准确的结果。 该项目的总体目标是开发一种护理点 (POC) 测试，用于测量患者的健康状况 坚持 PrEP 方案并最终预防已知有感染风险的人群感染 HIV 接触。 POC 测试将基于实验室质谱尿液测试，以检测 替诺福韦是 UrSure 已经开发的 PrEP 药物之一。 POC 检测会更快（几分钟即可 获得结果），因此可以在诊所就诊期间用于衡量 PrEP 依从性，如果合适的话， 向患者提供如何提高依从性的建议。第一阶段项目的目标是：1）综合四个 替诺福韦衍生物并将它们缀合形成两种免疫原，用于目标 2 中的多克隆抗体生产 以及目标 3 中用于 ELISA 的两种 HRP 缀合蛋白； 2) 产生两种亲和纯化的多克隆抗体 针对目标 1 中产生的两种免疫原中的每一种； 3) 使用这些开发原型 ELISA 衍生物和抗体，将用替诺福韦阳性和阴性的尿液样本进行验证。 该一期项目的最终成果将是缀合替诺福韦衍生物、多克隆抗体 这些衍生物的抗体和 ELISA，所有这些都将用于开发单克隆抗体和 最终在随后的 II 期应用中进行侧流免疫分析 POC 尿液替诺福韦测试。这 第一阶段项目将是开发 POC 尿液检测的关键一步，并带来一个强大的工具 推动全球医生坚持 PrEP 并减少 HIV 感染的能力。