Tel-Me-Box: Validating and testing a novel, low-cost, real-time monitoring device with hair level analysis among adherence-challenged patients

 描述（由申请人提供）：鉴于自我报告依从性、药丸计数和药物电子监测系统（MEMS）上限的众所周知的局限性，迫切需要真实的实时监测HIV治疗依从性的新型有效方法。为了在资源丰富和资源有限的情况下都能推广和可持续，这种装置需要成本低，设计方式不会增加艾滋病毒意外泄露和随后污名化的风险。既能真实的实时监测依从性，又能为患者提供量身定制的服药提醒的设备，有可能大大提高对艾滋病毒治疗以及其他慢性病治疗的依从性。我们的印度-美国合作团队十多年来一直在进行关于艾滋病毒污名化、抗逆转录病毒药物依从性模式和障碍、治疗结果和耐药性的研究。我们还率先使用少量头发样本中的抗逆转录病毒药物浓度来测量资源丰富和有限环境（RLS）中的长期抗逆转录病毒药物依从性。为了满足对新型依从性测量的需求，我们的团队最近开发了Tel-Me-Box，这是一种小型，低成本的依从性设备，通过打开时向服务器发送无线信号来真实的监控依从性。我们现在建议增加硬件，使服务器软件能够对设备进行无线编程，以便在一段时间不活动后激活定制的服药提醒（通过蜂鸣声，振动或LED灯）。该设备可以放在口袋里，可以容纳1-2周的药物，电池寿命长，充电能力简单，并且在试点研究中发现印度患者可以接受依从性挑战。由于艾滋病毒的耻辱感在包括印度在内的许多环境中是坚持抗逆转录病毒治疗的一个深刻障碍，Tel-Me-Box的小而不显眼的性质，沿着其提供量身定制的提醒功能的能力，尊重了参与者的隐私问题。 由于这种电子设备监测无法评估实际的药物摄入，因此根据生物学测量方法（如ARV毛发浓度）对其进行验证至关重要。这项研究有以下3个目标：目标1将进一步完善Tel-Me-Box，缩小其大小，并增加定制的 提醒功能。我们还将通过培训当地工作人员进行相关的毛发分析来证明在RLS中进行毛发分析的可行性。目标2将使用ARV毛发浓度和HIV病毒载量验证Tel-Me-Box依从性测量，并检查Tel-Me-Box监测和毛发药物水平对HIV感染患者病毒学抑制的预测效用。在目标3中，我们将进行一项试点RCT，以检查可接受性和可行性，并估计自动定制的实时依从性提醒对头发ARV浓度、器械监测依从性和依从性挑战患者的病毒载量抑制的效应量。在研究完成时，我们预计已经验证了Tel-Me-Box作为一种创新工具，可以评估依从性和预测治疗结果，并证明了RLS中头发分析的可行性。如果成功，我们还将为未来的大规模RCT收集有关Tel-Me-Box自动定制提醒的有效性的试点数据。

 DESCRIPTION (provided by applicant): Novel, validated methods to monitor adherence to HIV treatment in real time are urgently needed given the well-known limitations of self-reported adherence, pill counts, and medication electronic monitoring system (MEMS) caps. In order to be scalable and sustainable in both resource-rich and resource limited settings, such devices need to be low-cost and designed in a way that does not increase the risk of accidental HIV disclosure and subsequent stigma. Devices which both monitor adherence in real time and provide tailored reminders to patients for medication-taking have the potential to greatly improve adherence to HIV treatment as well as to treatment for other chronic diseases. Our Indo-US collaborative team has been conducting research on HIV stigma, ARV adherence patterns and barriers, treatment outcome, and drug resistance for over a decade. We have also pioneered the use of ARV concentrations in small hair samples to measure long-term ARV adherence in resource-rich and limited settings (RLS). In response to the need for novel adherence meaures, our team has recently developed Tel-Me-Box, a small, low-cost adherence device that monitors adherence in real time, by transmitting a wireless signal to a server when opened. We now propose to add hardware that will enable the server software to wirelessly program the device to activate tailored medication-taking reminders (via a beep, vibration, or LED light) after a period of inactivity. The device fits in a pocket, can hold 1-2 weeks' worth of medications, has a long battery life, simple charging capability, and has been found acceptable to Indian patients with adherence challenges in pilot studies. Since HIV stigma serves as a profound barrier to ARV adherence in many settings, including India, the small, inconspicuous nature of Tel-Me-Box, along with its ability to deliver tailored reminder features honors participants' privacy concerns. Since this electronic device monitoring cannot assess actual drug ingestion, validating it against a biological measure of adherence, such as ARV hair concentrations, is crucial. This study has the following 3 aims: Aim 1 will further refine Tel-Me-Box by reducing its size and adding tailored reminder features. We will also demonstrate feasibility of hair analysis in RLS by training local staff to conduct the relevant hair assays. Aim 2 will validate the Tel-Me-Box adherence measure, using ARV hair concentrations and HIV viral load, and examine the predictive utility of Tel-Me-Box monitoring and hair drug levels on virologic suppression in HIV- infected patients. In Aim 3, we will conduct a pilot RCT to examine acceptability and feasibility and to estimate the effect size of automated tailored real-time adherence reminders on hair ARV concentrations, device- monitored adherence, and viral load suppression in adherence-challenged patients. At study completion, we expect to have validated Tel-Me-Box as an innovative tool to assess adherence and predict treatment outcomes and demonstrated the feasibility of hair analyses in RLS. If successful, we will also have collected pilot data on the efficacy of the Tel-Me-Box automated, tailored reminders for a future large scale RCT.