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

项目摘要 艾滋病毒仍然是一种危险的流行疾病，在全球范围内造成数百万人感染和 每年的死亡人数和数百亿美元的医疗费用。特鲁瓦达作为预曝光的使用 预防(PrEP)如果每天服用，在预防艾滋病毒感染方面是99%有效的，但它对减少艾滋病毒感染的影响 负担受到遵守不力的限制。PREP是由疾病控制中心(CDC)在年推荐的 已知的艾滋病毒感染高危人群，包括男男性行为者，患有艾滋病的人 性传播感染史，静脉注射吸毒者，以及与HIV阳性伴侣的人。药物监测 众所周知，依从性可以改善药物依从性，但目前还没有可用于依从性的商业产品 PrEP的监测。因此，对一种工具的迫切需求尚未得到满足，该工具将允许医生监测 他们的患者坚持使用PrEP。为了在常规的基础上被患者接受，并在 医生的工作流程，这种依从性测试需要是非侵入性的、无痛的、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将测量患者的护理点(POC)测试 坚持PrEP方案，最终防止已知有感染风险的人感染艾滋病毒 曝光。POC测试将以实验室为基础的质谱仪尿液测试为基础 替诺福韦，PrEP中的药物之一，UrSure已经开发。PoC分析将更快(几分钟到 获得结果)，因此可在临床访问期间用于测量PrEP依从性，并且如果适当， 就如何提高患者的依从性向患者提供咨询。这一阶段项目的目标是：1)合成四个 替诺福韦衍生物及其偶联形成两种免疫原，用于在AIM 2中生产多克隆抗体 2)制备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；以及3)利用这些 衍生物和抗体，将用替诺福韦阳性和阴性的尿样进行验证。 这一第一阶段项目的最终成果将是结合的替诺福韦衍生物，多克隆 这些衍生物的抗体和一种ELISA法，所有这些都将被用来开发单抗和 最终，在随后的第二阶段应用中进行侧向流动免疫分析POC尿替诺福韦试验。这 第一阶段项目将是开发我们的POC尿液测试的关键一步，并带来一个强大的工具 推动遵守PrEP的能力，并减少世界各地医生的艾滋病毒感染。

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.