Development of a urine-based point-of-care test for adherence to antiretroviral drugs

开发基于尿液的即时护理测试以检测抗逆转录病毒药物的依从性

基本信息

批准号：
9039935
负责人：
Saye Khoo
金额：
$ 58.52万
依托单位：
MAGEE-WOMEN'S RES INST AND FOUNDATION
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-12-10 至 2019-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9039935
关键词：
AIDS clinical trial group Adherence Affinity Africa South of the Sahara Algorithms Anti-Retroviral Agents Antibodies Antigens Area Bedside Testings Binding Bioinformatics Biological Assay Characteristics Chemistry Clinic Clinical Clinical Research Clinical Trials Collaborations Color Coupled Data Development Devices Diagnostic Diagnostic tests Dose Drug Monitoring Drug Targeting Effectiveness Elements England Equilibrium Evaluation Event Failure Glucuronides HIV HIV Infections Hospitals Impairment Individual Kidney Laboratories Lateral Lead Libraries Malaria Measurable Measures Methodology Modification Nucleic Acids Operative Surgical Procedures Outpatients Output Patients Performance Pharmaceutical Preparations Plasma Prevention Process Prophylactic treatment Proteins Proteinuria Public Health Reaction Recruitment Activity Research Research Design Saliva Sampling Sampling Studies Shipping Ships Signal Transduction Specificity Staging Surveys Tail Tenofovir Testing Therapeutic Translating Treatment outcome Urine Visual antiretroviral therapy aptamer base comparative drug testing forgiveness healthy volunteer high throughput screening improved innovation laboratory equipment novel oral HIV point of care point-of-care diagnostics programs prototype public health relevance scaffold screening small molecule urinary

项目摘要

DESCRIPTION (provided by applicant): Non-adherence to antiretroviral therapy is a pervasive problem that limits the effectiveness of these drugs in both the treatment and pre-exposure prophylaxis of HIV infection. Although therapeutic drug monitoring (TDM) can be used to characterize adherence to antiretroviral therapy, current approaches are expensive and often require shipping samples to centralized laboratories. The expense, operational challenges, and delays associated with TDM limits the utility of this approach especially in the developing world. In our application, we propose to develop an aptamer based urine or saliva point-of-care (POC) diagnostic that could be used to detect antiretroviral drugs in these respective matrices. Development of a urine based POC that did not require expensive laboratory equipment and that could provide instantaneous results would be highly innovative and represent a significant paradigm shift in TDM. In addition, the chemistry and process research that underpins this proposal has novel elements but if successful would also be broadly applicable to many other therapeutic areas. Our specific aims in this application are as follows. Specific Aim 1 is to isolae and screen candidate aptamers for their ability to recognise key antiretrovirals used in treatment and prevention of HIV infection. Specific Aim 2 is to develop and evaluate readout platforms for incorporation into a prototype test device. Specific Aim 3 is to conduct a "tail" study to characterize the performance characteristics of the aptamer diagnostic in urine samples collected after cessation of dosing with antiretrovirals. Collectively, these specific aims would generate a prototype product that could be transferred to a diagnostics company for commercial development.

描述（由申请人提供）：不坚持抗逆转录病毒治疗是一个普遍存在的问题，限制了这些药物在 HIV 感染的治疗和暴露前预防中的有效性，尽管治疗药物监测 (TDM) 可用于表征依从性。对于抗逆转录病毒治疗，目前的方法价格昂贵，并且通常需要将样本运送到集中实验室，与 TDM 相关的费用、操作挑战和延迟限制了这种方法的实用性，尤其是在发展中国家。在我们的应用中，我们建议开发一种基于适体的尿液或唾液即时诊断（POC），可用于检测这些各自基质中的抗逆转录病毒药物。开发基于尿液的POC，不需要昂贵的实验室设备，并且能够提供即时结果将是高度创新的，代表了 TDM 的重大范式转变。此外，支持该提案的化学和工艺研究具有新颖的元素，但如果成功，也将广泛适用于我们的许多其他治疗领域。这个应用程序具体目标 1 是分离和筛选候选适体，以确定其识别用于治疗和预防 HIV 感染的关键抗逆转录病毒药物的能力。具体目标 2 是开发和评估用于纳入原型测试设备的读出平台。 3是进行“尾部”研究，以表征停止服用抗逆转录病毒药物后收集的尿液样本中适体诊断的性能特征，这些具体目标将共同产生。可以转移给诊断公司进行商业开发的原型产品。