Simplifying HIV Treatment and Monitoring (STREAM2): Point-of-Care Urine Tenofovir Adherence and Viral Load Testing to Improve HIV Outcomes in South Africa

摘要 对于接受抗逆转录病毒治疗(ART)的数百万艾滋病毒携带者(PLHIV)来说，足够的ART依从性 常规艾滋病毒病毒载量(VL)监测对于确保病毒抑制和良好的健康结果至关重要。 在低收入和中等收入国家(LMIC)发起和管理终身艺术对这两个国家都是一个挑战 PLHIV和提供者部分由于依赖于自我报告的遵守和基于实验室的VL测试的延迟， 这是日常护理的一部分。德雷恩博士和加勒特博士(联合首席调查员)最近完成了一项试验 南非的一项研究表明，接受基于efavirenz的PLHIV的护理点(POC)VL监测 与12个月相比，ART使VL抑制和护理保留增加了14%(95%可信区间6-21%) 到标准的实验室检测。然而，这些发现在更新、更稳健的背景下的适用性 包括南非在内的几个LMIC正在引入基于多洛替格列韦的ART方案，目前尚不清楚。至 作为POC VL监测的补充，我们最近完成了一款新型的 POC尿替诺福韦检测，与雅培诊断公司合作，可以监测临床上的ART依从性- 基于实时设置。基于我们的试点研究结果，我们在此应用程序中的目标是确定 使用POC替诺福韦实施HIV综合护理模式的临床疗效和成本效益 依从性测试和POC VL监测在维持PLHIV感染者持续VL抑制中的作用 以替诺福韦为基础的南非艺术。我们的中心假设是POC替诺福韦依从性试验和POC VL监测将提高VL抑制率和护理保留率，同时是一种可行、可接受和 具有成本效益的艺术管理策略。我们将用三个具体的例子来客观地检验我们的中心假设 目的：(1)确定使用POC替诺福韦依从性试验和 POC VL测试将改善VL抑制和护理中的保留；(2)监测实施情况并评估患者 以及供应商对南非的实时POC替诺福韦依从性测试和POC VL监测的看法； 以及(3)评估使用POC实施POC替诺福韦依从性测试的成本和成本效益 VL监测，与无客观依从性测试和基于实验室的VL监测相比。要完成这些任务 AIMS，我们将在ART开始时随机选择534名参与者(1：1)进行常规POC替诺福韦依从性测试 POC VL监测(ARM 1)或护理标准，无目标替诺福韦依从性测试和基于实验室的VL 监控(ARM 2)。参与者将被跟踪比较VL抑制的主要综合结果 并在ART开始后18个月时保留在研究臂之间的护理。这个随机对照 实施试验将提供有关临床疗效、可接受性和成本效益的关键数据 POC遵守和VL测试的集成模型，为改善LMIC中艾滋病毒护理的全球政策提供信息。

ABSTRACT For millions of people living with HIV (PLHIV) receiving antiretroviral therapy (ART), adequate ART adherence and routine HIV viral load (VL) monitoring are critical to ensure viral suppression and good health outcomes. Initiation and management of life-long ART in low- and middle-income countries (LMICs) is challenging for both PLHIV and providers in part due to the reliance on self-reported adherence and delays with lab-based VL testing, which are part of the usual care. Drs. Drain and Garrett (co-principal investigators) recently completed a pilot study in South Africa demonstrating that point-of-care (POC) VL monitoring for PLHIV receiving efavirenz-based ART increased VL suppression and retention in care by 14% (95% CI 6-21%) over a 12-month period compared to standard lab testing. However, the applicability of these findings to the context of newer, more robust dolutegravir-based ART regimens being introduced in several LMICs, including South Africa, is not known. To complement POC VL monitoring, we have recently completed the development and initial evaluation of a novel POC urine tenofovir assay, in collaboration with Abbott Diagnostics, which can monitor ART adherence in clinic- based settings in real-time. Building on our pilot study results, our objective in this application is to determine the clinical efficacy and cost effectiveness of implementing an integrated HIV care model using POC tenofovir adherence testing and POC VL monitoring in maintaining durable VL suppression among PLHIV receiving tenofovir-based ART in South Africa. Our central hypotheses are that POC tenofovir adherence testing and POC VL monitoring will improve VL suppression rates and retention in care, while being a feasible, acceptable, and cost-effective strategy for ART management. We will objectively test our central hypotheses with three specific aims: (1) to determine if an integrated model for HIV monitoring using a POC tenofovir adherence assay and a POC VL test will improve VL suppression and retention in care; (2) to monitor implementation and assess patient and provider perspectives of real-time POC tenofovir adherence testing and POC VL monitoring in South Africa; and (3) to estimate the costs and cost-effectiveness of implementing POC tenofovir adherence testing with POC VL monitoring, compared to no objective adherence testing and lab-based VL monitoring. To complete these aims, we will randomize 534 participants (1:1) at ART initiation into regular POC tenofovir adherence testing with POC VL monitoring (Arm 1) or standard-of-care with no objective tenofovir adherence testing and lab-based VL monitoring (Arm 2). Participants will be followed to compare a primary composite outcome of VL suppression and retention in care between the study arms at 18 months after ART initiation. This randomized controlled implementation trial will provide crucial data on the clinical efficacy, acceptability, and cost-effectiveness of an integrated model of POC adherence and VL testing to inform global policy on improving HIV care in LMICs.