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

 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，限制了这些药物在治疗和暴露前预防HIV感染方面的有效性。虽然治疗药物监测（TDM）可用于表征抗逆转录病毒治疗的依从性，但目前的方法价格昂贵，并且通常需要将样本运送到中心实验室。与TDM相关的费用、运营挑战和延迟限制了这种方法的实用性，特别是在发展中国家。在我们的申请中，我们提出开发一种基于适体的尿液或唾液床旁（POC）诊断，其可用于检测这些相应基质中的抗逆转录病毒药物。不需要昂贵的实验室设备并且可以提供即时结果的基于尿的POC的开发将是高度创新的，并且代表TDM的显著范式转变。此外，支持这一建议的化学和过程研究具有新颖的元素，但如果成功，也将广泛适用于许多其他治疗领域。我们在本申请中的具体目标如下。具体目标1是分离和筛选候选适体，以识别用于治疗和预防HIV感染的关键抗逆转录病毒药物。具体目标2是开发和评估纳入原型测试设备的读出平台。具体目标3是进行“尾部”研究，以表征停止抗逆转录病毒药物给药后采集的尿样中适体诊断的性能特征。总的来说，这些具体目标将产生一个原型产品，可以转移到诊断公司进行商业开发。

 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.