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

尿液替诺福韦即时检测可识别需要 ART 依从性支持的患者

• 批准号: 9983237
• 负责人: Monica Gandhi
• 金额: $ 34.35万
• 依托单位: STELLENBOSCH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-07 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9983237
• 关键词: Adherence; Aftercare; Agreement; Anti-Retroviral Agents; Antibodies; Bedside Testings; Biological Assay; Blood; California; Caring; Client satisfaction; Clinic; Clinic Visits; Clinical; Counseling; Cross-Sectional Studies; Development; Diagnostic; Diphosphates; Drug resistance; Enrollment; Failure; Feedback; Grant; Guidelines; HIV; HIV-1; Hair; Health; Health Personnel; Immunoassay; Immunologics; Individual; Intervention; Interview; Laboratories; Lamivudine; Length of Stay; Measures; Modernization; Monitor; Outcome; Participant; Patient Recruitments; Patient Self-Report; Patients; Perception; Pharmaceutical Preparations; Pharmacy facility; Plasma; Primary Health Care; Process; Provider; Psychological reinforcement; Questionnaires; Ramp; Randomized Controlled Trials; Regimen; Resistance; Resources; Risk; Sampling; San Francisco; Scientist; Service delivery model; Services; South Africa; South African; Specificity; Spottings; Supervision; Surveys; Technology; Tenofovir; Testing; Time; Treatment Failure; Underrepresented Groups; Universities; Urine; Vertebral column; Viral Load result; Viral load measurement; Visit; antiretroviral therapy; arm; base; behavioral adherence; care systems; compliance behavior; cost; design; follow-up; high risk; improved; improved outcome; instrumentation; intervention participants; novel; point of care; prevent; primary outcome; randomized controlled study; secondary outcome; side effect; standard of care; success; support tools; therapy adherence; tool; transmission process; treatment adherence; treatment arm; viral resistance; virology

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.

项目摘要 需要足够遵守组合抗逆转录病毒疗法（ART）来抑制HIV病毒负荷 患有艾滋病毒的人，这对于个人级别的利益和防止前进至关重要 艾滋病毒的传播。虽然较新的艺术方案的耐受性更好，但副作用较少，较低的风险 耐药性比较旧的方案，治疗成功仍然取决于患者的依从性。 当前识别依从性不足的方法是主观的或不敏感的，而目标 头发，干斑或血浆中治疗暴露的标记（药物水平）需要昂贵 仪器，因此不可扩展。作为治疗的最终目的是实现HIV病毒负荷 抑制，使用HIV病毒负荷测试的使用正在全球范围内扩展。由于它仍然是一项昂贵的测试，所以 通常很少执行，因此迟到了治疗失败，导致错过的机会 提高依从性。在诊所客观地评估对ART的依从性评估依从性的低成本护理（POC）评估 在资源有限的设置（RLS）中，访问可以：1）提供有关最近依从性的立即信息 然后可以得到适当的依从性支持； 2）允许更频繁地评估依从性 并加强病毒学衰竭之前的适当依从性行为； 3）区分患者 由于耐药性较差而导致的病毒学衰竭。最后，随着目前的推出 Tenofovir，Lamivudine和Dolutegravir（TLD）在RLS中，故障率预计较低且阻力很少， 必须采用监测策略，主要是识别依从性不足的患者。 最近，加利福尼亚大学旧金山（UCSF）头发分析实验室和Abbott™Rapid 诊断已经开发了一种基于尿液的Tenofovir（TFV）的免疫测定法。这种基于抗体的测定检测 尿液中TFV的存在准确，易于执行，既低成本（每次测试<$ 2美元），又是点 - 医疗（POC），允许立即向患者和提供者遵守反馈。 因此，我们将进行以下目的进行研究：1）研究基于尿液的替诺福韦的能力 快速评估（UTRA）在横截面研究中检测病毒衰竭，以及UTRA的关联 在干血点（120例患者）中测量的自我报告的依从性和长期TFV暴露； 2） 定性评估UTRA在患者（25）和卫生保健工作者（5）中的可接受性； 3）执行飞行员 依从性挑战患者之间的随机对照研究，以研究有用性，可行性和 与护理咨询的标准相比，UTRA支持的依从性咨询的可接受性 长期的HIV病毒负荷结果（每只手臂中有100例患者）。设想的总体影响是，按研究端， 我们希望能在资源中验证这种新型的基于尿液的实时尿液治疗依从性监测工具 有限的设置，并为更大的试验提供了触发立即依从性支持和评估更昂贵的试验 实验室测试，使用实践POC测试，以改善全球长期病毒学结果。