Measuring and Monitoring Adherence to ART with Pill Ingestion Sensor System

 描述(申请人提供)：抗逆转录病毒疗法(ART)的引入已经将艾滋病毒感染从一种致命的疾病转变为可控制的疾病，但坚持抗逆转录病毒疗法对于优化结果仍然至关重要。现有的ART依从性指标，如自我报告、药片计数、电子药瓶盖和处方再灌装，仅提供实际药物摄入量的推断指标，大多数没有提供实时通知功能。直接观察疗法衡量的是实际的药物摄入量，但并不实用。这些限制限制了对服药依从性的研究，更重要的是，限制了我们基于对艾滋病毒感染者依从性的可行的体内监测来开发实时干预以促进服药的能力。Proteus数字健康系统(PDHF)是由Proteus Digital Health开发的基于药片可摄入传感器的依从性测量和监控系统，解决了这些限制。它涉及到使用可摄取传感器，这是一种微小的可食用材料，我将其与处方药物一起过度封装。该传感器通过摄取激活，并通过患者佩戴的带有嵌入式监视器和传感器的贴片来感知。监控器向移动设备发送蓝牙信号，移动设备继而向中央服务器发送加密消息，从而实现对已服用剂量的实时监控。我们建议开发一个数据接收中心，并在这些组件中添加一条自动文本消息，当错过一剂药物时，该消息会发送给患者。这种可摄取的传感器和贴片监测系统已经获得FDA的批准，是安全的，但尚未在临床环境中在艾滋病毒感染患者中进行测试。这项研究的第一个目标是确认过包膜抗逆转录病毒药物(ARV)的生物利用度，并在15名参与者中试行PDHF系统的使用，以测试和确定优化这一测量和监测系统使用的方法。下一个目标是确定该系统在促进抗逆转录病毒治疗依从性方面的可行性、可接受性、可持续性、准确性和有效性。可行性、可接受性和可持续性将通过患者对该系统的评分和使用该系统的辍学率进行评估。准确性将通过PDHF系统测量的对抗逆转录病毒治疗的依从性与其他依从性测量之间的关联来评估，例如血浆药物水平、抗逆转录病毒药物浓度和自我报告。疗效将通过比较被分配到PDHF系统的参与者和被分配到日常护理(UC)的参与者随着时间的推移与病毒载量和CD4的探索性结果进行评估。我们将招募120名18岁或18岁以上的艾滋病毒感染患者，他们的依从性不佳。参与者将被随机接受为期16周的PDHF系统或UC，每月进行评估。PDHF系统在停止使用后的效果的持久性将在12周的后续阶段中确定。总而言之，我们将评估使用PDHF系统的可行性、可接受性和可持续性；评估PDHF系统在衡量遵守ART方面的准确性；以及评估PDHF系统在监测和利用遵守ART方面的效果。1

 DESCRIPTION (provided by applicant): Introduction of antiretroviral therapy (ART) has transformed HIV-infection from a fatal to manageable disease but adherence to ART remains critical to optimize outcomes. Existing measures of ART adherence such as self-report, pill counts, electronic pill-bottle caps, and prescription refills, provide only inferred measures of actual drug intake and most offer no real-time notification capability. Directly observed therapy measures actual drug intake but is not practical. These limitations constrain research into medication adherence and more importantly, limit our ability to develop real-time interventions based on feasible, in vivo monitoring of adherence among HIV-infected people to facilitate medication-taking. The Proteus digital health feedback (PDHF) system, a pill ingestible sensor based adherence measuring and monitoring system developed by Proteus Digital Health, addresses these limitations. It involves use of an ingestible sensor, a tiny edible material that i over-encapsulated along with prescribed medication. The sensor is activated by ingestion and is sensed by a patch worn by the patient with an embedded monitor and sensor. The monitor sends a Bluetooth signal to a mobile device, which in turn sends an encrypted message to a central server, thus effecting real-time monitoring that a dose has been taken. We propose to develop a data receiving hub and add to these components an automated text message that is sent to the patient when a dose is missed. The ingestible sensor and patch monitor system is already FDA-approved as safe, but has yet to be tested in HIV- infected patients in clinical setting. The first goals of this study are to confirm the bioavailability of over- encapsulated antiretrovirals (ARVs) and to pilot-test the use of the PDHF system in 15 participants prescribed ARVs to test and identify approaches that optimize the use of this measuring and monitoring system. The next goals are to determine the system's feasibility, acceptability, sustainability, accuracy and efficacy in fostering ART adherence. Feasibility, acceptability and sustainability will be assessed by patients' rating of the system and the rate of dropping off from using the system. Accuracy will be evaluated by the associations between adherence to ART measured by the PDHF system and other adherence measures such as plasma drug level concentrations of ARVs and self-report. Efficacy will be assessed by comparing adherence of participants assigned to the PDHF system and participants assigned to usual care (UC) over time, with exploratory outcomes of viral load and CD4. We will recruit 120 of HIV-infected patients 18 years or older with sub-optimal adherence. Participants will be randomized to receive the PDHF system or UC for 16 weeks with monthly assessments. The durability of effects of the PDHF system after stopping the use of the system will be determined during a 12-week follow-up stage. In summary, we will evaluate the feasibility, acceptability and sustainability of using the PDHF system; assess the accuracy of the PDHF system in measuring adherence to ART; and evaluate the efficacy of the PDHF system for monitoring and leveraging adherence to ART. 1