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)：鉴于自我报告的依从性、药片计数和药物电子监测系统(MEMS)上限的众所周知的局限性，迫切需要新的、有效的方法来实时监测艾滋病毒治疗的依从性。为了在资源丰富和资源有限的情况下都具有可伸缩性和可持续性，这种设备需要低成本，并以不增加意外披露艾滋病毒和随后的耻辱的风险的方式设计。既实时监测依从性，又为患者服药提供量身定制的提醒的设备，有可能极大地提高对艾滋病毒治疗以及其他慢性病治疗的依从性。十多年来，我们的印美合作团队一直在进行关于艾滋病毒污名、抗逆转录病毒依从性模式和障碍、治疗结果和耐药性的研究。我们还率先使用小样本中的抗逆转录病毒浓度来衡量在资源丰富和有限的环境(RLS)中抗逆转录病毒的长期依从性。为了应对对新的依从性手段的需求，我们的团队最近开发了一种小型、低成本的依从性设备TEL-Me-Box，它通过在打开时向服务器传输无线信号来实时监控依从性。我们现在建议添加硬件，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(通过嘟嘟声、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，在试点研究中发现印度患者对依从性有挑战的患者可以接受。由于艾滋病毒的污名在包括印度在内的许多环境中是坚持抗逆转录病毒病毒的严重障碍，tel-Me-Box的小而不引人注目的性质，以及其提供定制提醒功能的能力，尊重了参与者的隐私担忧。 由于这种电子设备监测无法评估实际的药物摄入量，因此对照ARV毛发浓度等生物依从性指标进行验证是至关重要的。这项研究有以下三个目标：目标1将通过缩小尺寸和增加定制的方式来进一步提炼TeleMe-Box 提醒功能。此外，我们亦会培训本地员工进行相关的头发分析，以示范在研究中心进行头发分析的可行性。AIM 2将使用ARV毛发浓度和HIV病毒载量来验证tel-me-Box依从性测量，并检查tel-me-Box监测和头发药物水平对HIV感染患者的病毒学抑制的预测效用。在目标3中，我们将进行一项试验性随机对照试验，以检查可接受性和可行性，并估计自动定制实时依从性提醒对依从性挑战患者的毛发ARV浓度、设备监控依从性和病毒载量抑制的影响大小。在研究完成时，我们预计将验证tel-me-Box作为评估依从性和预测治疗结果的创新工具，并证明头发分析在RLS中的可行性。如果成功，我们还将收集关于tel-me-Box自动化、量身定做的提醒的有效性的试点数据，以供未来大规模的RCT使用。

 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.