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

项目总结 需要足够的联合抗逆转录病毒疗法(ART)来抑制HIV病毒载量 艾滋病毒携带者，这对个人层面的利益和防止艾滋病毒继续传播是必不可少的 艾滋病毒的传播。虽然新的ART方案耐受性更好，但副作用更少，风险更低 尽管与旧方案相比耐药，但治疗成功仍取决于患者的依从性。 目前确定遵守不充分的方法要么是主观的，要么是不敏感的，而客观的 头发、干血斑点或血浆中的治疗暴露(药物水平)标记物需要昂贵 工具，因此不可伸缩。因为治疗的最终目的是达到HIV病毒载量 除了抑制，艾滋病毒病毒载量检测的使用正在世界范围内推广。由于它仍然是一项昂贵的测试，它是 通常不经常进行，因此发现治疗失败的时间较晚，导致错失了治疗机会 提高遵从性。临床上客观评估抗逆转录病毒治疗依从性的低成本护理点(POC)分析 在资源受限设置(RLS)中的访问可以：1)提供有关最近遵守的即时信息 随后可提供适当的遵从性支持；2)允许更频繁地评估遵从性 并在病毒学失败之前加强适当的坚持行为；3)区分患者 由于耐药者对病毒的依从性差而导致病毒学失败。最后，随着目前推出的 替诺福韦、拉米夫定和多洛替格韦(TLD)在RLS中，失败率预计很低，耐药性很少， 有必要制定一项监测策略，主要侧重于识别依从性不足的患者。 最近，加州大学旧金山分校的头发分析实验室和雅培™快速 诊断公司已经开发出一种基于尿液的替诺福韦(TFV)免疫分析方法。这种基于抗体的检测方法可以检测到 TFV在尿液中的存在准确，易于操作，而且成本低(每次检测2美元)，而且 Of-care(POC)，允许立即向患者和提供者提供依从性反馈。 因此，我们将进行一项旨在以下目的的研究：1)考察尿基替诺福韦的能力 一项横断面研究中检测病毒学故障的快速检测(UTRA)，以及UTRA与 自我报告的依从性和长期接触TFV的干血斑(120名患者)； 定性评估UTRA在患者(25人)和医护人员(5人)中的可接受性；3)进行试点 在依从性挑战患者中进行的随机对照研究，以考察其有效性、可行性和 与标准护理咨询相比，UTRA支持的依从性咨询对影响的可接受性 艾滋病毒病毒载量的长期结果(每组100名患者)。预计的总体影响是，到研究结束时， 我们希望已经在一个资源中验证了这个基于尿液的新型实时治疗依从性监测工具- 有限的设置，并通知较大的试验以触发立即依从性支持和更昂贵的配给 实验室检测，使用实用的POC检测，以改善全球病毒学的长期结果。

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.