Urine tenofovir point-of-care test to identify patients in need of ART adherence support

项目摘要 需要充分坚持联合抗逆转录病毒治疗（ART），以抑制艾滋病毒载量， 艾滋病毒感染者，这对于个人层面的福利和预防未来的艾滋病毒感染至关重要。 艾滋病毒的传播。虽然较新的ART方案耐受性更好，副作用更少， 尽管药物耐药性比旧的治疗方案高，但治疗成功仍然取决于患者的依从性。 目前识别依从性不足的方法要么主观，要么不敏感，而客观 毛发、干血斑或血浆中的治疗暴露标记（药物水平）需要昂贵的 仪器，因此不可扩展。由于治疗的最终目的是达到HIV病毒载量 随着艾滋病病毒感染率的下降，艾滋病毒载量检测的使用正在全球范围内扩大。由于它仍然是一个昂贵的测试， 通常很少进行，因此治疗失败被发现较晚，导致错过机会， 改善粘附性。一种低成本的床旁（POC）检测方法，用于客观评估临床对ART的依从性 在资源有限的情况下（RLS），访问可以：1）提供有关最近遵守的即时信息， 然后，可以提供适当的依从性支持; 2）允许更频繁地评估依从性 并在病毒学失败发生前加强适当的依从行为; 3）区分患者 由于耐药性患者的依从性差，导致病毒学失败。最后，随着目前推出的 替诺福韦、拉米夫定和度鲁特韦（dolutegravir，dolutegravir）治疗RLS，失败率预计较低，耐药罕见， 需要主要集中于识别依从性不足的患者的监测策略。 最近，加州大学旧金山弗朗西斯科（UCSF）毛发分析实验室和Abbott™ Rapid 诊断已经开发了一种基于尿液的替诺福韦（TFV）免疫测定。这种基于抗体的检测方法检测 尿液中TFV的存在准确，易于执行，并且成本低（每次测试<2美元）和点- 护理外（POC），允许立即向患者和提供者提供依从性反馈。 因此，我们将进行一项研究，其目的如下：1）研究尿基替诺福韦的能力 沿着UTRA与病毒学失败的关联， 自我报告的依从性和长期TFV暴露，以干血斑测量（120例患者）; 2） 定性评估UTRA在患者（25）和医护人员（5）中的可接受性; 3）进行试点 在依从性挑战患者中进行的一项随机对照研究，旨在研究 UTRA支持的依从性咨询的可接受性，与标准护理咨询相比， 长期HIV病毒载量结果（每组100例患者）。预期的总体影响是，到研究结束时， 我们希望已经验证了这种新的实时尿基治疗依从性监测工具，在一个资源- 有限的设置，并通知一个更大的试验，以触发立即遵守支持和配给更昂贵 实验室检测，使用实际的POC测试，以改善全球的长期病毒学结果。

PROJECT SUMMARY Adequate adherence to combination antiretroviral therapy (ART) is required to suppress HIV viral loads among individuals living with HIV, which is essential both for individual-level benefits and to prevent the onward transmission of HIV. While newer ART regimens are better tolerated, have fewer side effects and a lower risk of drug resistance than older regimens, treatment success nevertheless remains dependent on patient adherence. Current approaches to identify inadequate adherence are either subjective or insensitive, whereas objective markers of treatment exposure (drug levels) in hair, dried blood spots or plasma require expensive instrumentation and are therefore not scalable. As the ultimate aim of treatment is to achieve HIV viral load suppression, use of HIV viral load testing is being expanded worldwide. As it remains an expensive test, it is often performed infrequently and therefore treatment failure is detected late, resulting in missed opportunities to improve adherence. A low-cost point-of-care (POC) assay to assess adherence to ART, objectively at clinic visits, in resource limited settings (RLS), could: 1) Provide immediate information on recent adherence which can then be followed with appropriate adherence support; 2) Allow for more frequent assessment of adherence and reinforcement of appropriate adherence behavior before virologic failure occurs; 3) Differentiate patients with virological failure due to poor adherence from those with drug resistance. Finally, with the current roll-out of tenofovir, lamivudine and dolutegravir (TLD) in RLS, failure rates are expected to be low and resistance rare, necessitating a monitoring strategy primarily focused on identifying patients with inadequate adherence. Recently the University of California, San Francisco (UCSF) Hair Analytical Laboratory and Abbott™ Rapid Diagnostics has developed a urine-based immunoassay for tenofovir (TFV). This antibody-based assay detects the presence of TFV in urine accurately, is easy-to-perform, and is both low-cost (< $2 dollars per test) and point- of-care (POC), which allows for immediate adherence feedback to both patient and provider. We will therefore conduct a study with the following aims: 1) Investigate the ability of the urine-based tenofovir rapid assay (UTRA) to detect virologic failure in a cross-sectional study, along with the association of UTRA with self-reported adherence and long term TFV exposure as measured in dried blood spots (120 patients); 2) Qualitatively assess the acceptability of UTRA in patients (25) and health care workers (5); 3) Perform a pilot randomized controlled study among adherence-challenged patients to investigate the usefulness, feasibility and acceptability of UTRA-supported adherence counseling, compared to standard of care counseling, to impact long-term HIV viral load outcomes (100 patients in each arm). The envisaged overall impact is that by study end, we hope to have validated this novel real-time urine-based treatment adherence monitoring tool, in a resource- limited setting, and inform a larger trial to trigger immediate adherence support and ration more expensive laboratory testing, using the practical POC test, to improve long-term virologic outcomes worldwide.