Measuring and Monitoring Adherence to ART with Pill Ingestion Sensor System

 描述（由申请人提供）：抗逆转录病毒疗法（ART）的引入已将艾滋病毒感染从致命性疾病转变为可控制的疾病，但坚持ART对优化结果仍然至关重要。现有的抗逆转录病毒治疗依从性的测量方法，如自我报告、药丸计数、电子药丸瓶盖和处方续药，仅提供实际药物摄入量的推断测量，大多数没有提供实时通知能力。直接观察治疗测量实际药物摄入量，但不实用。这些局限性限制了对药物依从性的研究，更重要的是，限制了我们基于可行的、体内监测艾滋病毒感染者依从性以促进服药的实时干预措施的能力。Proteus数字健康反馈（PDHF）系统，由Proteus Digital Health开发的基于药丸可摄取传感器的依从性测量和监测系统，解决了这些限制。它涉及到使用一个可摄入的传感器，一个微小的可食用材料，我超过封装沿着与处方药。该传感器通过摄入激活，并通过患者佩戴的带有嵌入式监视器和传感器的贴片进行感测。监测器向移动终端发送蓝牙信号，移动终端又向中央服务器发送加密消息，从而实现对已经服用的剂量的实时监测。我们建议开发一个数据接收中心，并在这些组件中添加自动文本消息，当错过剂量时发送给患者。可摄取传感器和贴片监测系统已经被FDA批准为安全的，但尚未在临床环境中在HIV感染患者中进行测试。本研究的第一个目标是确认封装的抗逆转录病毒药物（ARV）的生物利用度，并在15名接受ARV处方的参与者中对PDHF系统的使用进行初步测试，以测试和确定优化使用该测量和监测系统的方法。下一个目标是确定该系统在促进抗逆转录病毒疗法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系统的评分和退出使用系统的比率来评估。将通过PDHF系统测量的抗逆转录病毒治疗依从性与其他依从性指标（如抗逆转录病毒药物的血浆药物水平浓度和自我报告）之间的相关性来评价准确性。将通过比较分配至PDHF系统的受试者和分配至常规治疗（UC）的受试者随时间的依从性以及病毒载量和CD 4的探索性结局来评估疗效。我们将招募120名18岁或以上的艾滋病毒感染患者，这些患者的依从性不佳。受试者将随机接受PDHF系统或UC治疗16周，每月进行一次评估。将在12周的随访阶段确定停止使用PDHF系统后该系统的效果持久性。总之，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系统在测量ART依从性方面的准确性;并评估PDHF系统监测和利用ART依从性的有效性。

 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