A competitive lateral flow assay for the detection of tenofovir

A competitive lateral flow assay for the detection of tenofovir
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DOI:
10.1016/j.aca.2018.02.039
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发表时间:
2018-08-09
影响因子:
6.2
通讯作者:
Klapperich, Catherine M.
Klapperich, Catherine M.
中科院分区:
化学1区
文献类型:
--
作者:
Pratt, George W.;Fan, Andy;Klapperich, Catherine M.

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艾滋病毒感染的适当管理要求患者至少80-95%遵守规定的药物治疗方案,以避免不良的健康结果和耐药性艾滋病毒株的发展。临床医生通常通过患者自我报告、药丸计数和电子药物监测间接监测依从性习惯。虽然直接测量尿液等患者样本以监测药物水平是可能的,但它需要专门的设备和培训,而在资源有限的环境中,这种设备和培训是不容易获得的。在这项工作中,我们报告了一种抗体的发展,结合替诺福韦(TFV),一个关键的小分子药物,用于治疗和预防艾滋病毒,和竞争性的侧流试验,使用该抗体来监测尿液样本中的药物的存在。将TFV与免疫原性蛋白结合并注射到兔子中以产生对药物敏感的多克隆抗体。通过免疫沉淀和HPLC验证抗体的TFV敏感性。开发了一种基于金纳米颗粒的竞争性检测方法,用于检测尿液样本中TFV的存在,灵敏度为1 μ g/mL(-1)。这种TFV检测可以作为一种即时设备部署,用于在资源有限的环境中进行依从性监测,作为当前方法的低成本,准确和快速的替代方案,以更好地告知治疗的变化。(C)2018爱思唯尔B. V.保留所有权利。
Proper management of an HIV infection requires that a patient be at least 80-95% adherent to a prescribed drug regimen to avoid poor health outcomes and the development of drug-resistant HIV strains. Clinicians generally monitor adherence habits indirectly through patient self-reporting, pill counting, and electronic drug monitoring. While direct measurement of patient samples like urine for monitoring drug levels is possible, it requires specialized equipment and training that is not readily available in resource-limited settings where the need is greatest. In this work we report the development of an antibody that binds to tenofovir (TFV), a key small molecule drug for both the treatment and prevention of HIV, and a competitive lateral flow assay that uses that antibody to monitor urine samples for the presence of the drug. TFV was conjugated to an immunogenic protein and injected into rabbits to raise polyclonal antibodies sensitive to the drug. The antibodies were verified for TFV-sensitivity by immunoprecipitation and HPLC. A gold nanoparticle-based competitive assay was developed to detect the presence of TFV in urine samples with a sensitivity of 1 mu g mL(-1). This TFV assay could be deployed as a point-of-care device for adherence monitoring in resource-limited settings as a low-cost, accurate, and speedy alternative to current methods to better inform changes in treatment. (C) 2018 Elsevier B.V. All rights reserved.