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危险且普遍的疾病，导致数百万感染和 每年死亡和数百亿美元的医疗费用。使用Truvada作为曝光前 预防（PREP）有效地有效预防每天预防艾滋病毒感染，但对减少艾滋病毒的影响 负担受到依从性不佳的限制。疾病控制中心（CDC）推荐PREP 众所周知的艾滋病毒感染风险很高，其中包括与男人发生性关系的男人，患有 性病，静脉吸毒者的历史以及患有艾滋病毒阳性的伴侣的人。监测药物 依从性众所周知可以提高药物合规性，但没有依从性的商业产品 预备监测。因此，对工具的迫切需求至关重要，该工具将允许医生监视 遵守患者的准备。为了日常患者可以接受，可行 医师工作流程，这种依从性测试需要无创，无痛，便宜，并提供 快速，准确的结果。 该项目的总体目标是开发一个护理点（POC）测试，该测试将测量患者 遵守准备方案，并最终防止已知有风险的人的艾滋病毒感染 接触。 POC测试将基于基于实验室的质谱尿液测试 Tenofovir是PREP中的一种药物之一，它已经开发出来。 POC分析的速度将更快（分钟为 得到结果），因此可以在诊所访问期间使用以衡量预依从性，并在适当的情况下使用 咨询患者如何提高其合规性。该阶段I项目的目的是：1）合成四个 Tenofovir衍生物并将它们偶联以在AIM 2中形成两种免疫原以用于多克隆抗体的产生 以及在AIM 3中使用ELISA的两个HRP偶联蛋白； 2）产生两种亲和力纯化的多克隆抗体 针对AIM 1中产生的两种免疫原子中的每一个； 3）使用这些开发原型ELISA 衍生物和抗体，将用Tenofovir呈阳性和阴性验证。 该阶段I项目的最终可交付成果将是共轭替诺福韦衍生物，多克隆 这些衍生物和ELISA的抗体，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，横向流量免疫测定POC尿液Tenofovir测试。这 第一阶段项目将是开发我们的POC尿液测试并带来强大工具的关键一步 推动预科依从性并减少艾滋病毒感染对全球医生的能力。