Digital adherence technologies to facilitate completion of short-course tuberculosis preventive therapy among people living with HIV

项目总结/摘要 结核病（TB）是艾滋病毒感染者（PLHIV）死亡的主要原因， 占全球艾滋病死亡人数的三分之一。结核病预防性治疗（TPT），可降低结核病发病率 30- 50%，是世界卫生组织（WHO）推荐的所有艾滋病毒感染者。虽然新的12剂， 每周一次的异烟肼和利福喷丁（3 HP）方案，通过直接观察治疗（DOT），现在是可用的 治疗的完成仍然是一个令人关切的问题。此外，DOT不是一个可行的策略， 增加高负担、低收入环境中结核病预防治疗的使用。为了实现 3 HP降低艾滋病毒感染者结核病死亡率的潜力，迫切需要进行研究， 通过自我管理疗法支持完成治疗的方法。 本提案的总体目标是确定低成本数字坚持技术（DAT） 可用于监测和支持艾滋病毒感染者完成3 HP。我们的中心假设是一个理论- 根据用户的需要对数据访问测试进行适当的调整，将导致数据访问测试的高水平采用和实施 忠诚这个假设是基于我在使用以人为中心的设计（HCD）的工作中获得的初步数据 调整DAT平台的方法，以解决活动性结核病患者面临的依从性挑战。在我 Mentor的阶梯式楔形随机试验，这种适应性DAT平台具有较高的可接受性， 患者和提供者，并改善活动性结核病的治疗完成情况。拟议的研究将建立 在此之前的工作，以支持使用DAT扩大结核病预防治疗的关键高风险， 人口为了检验目标1中的这一假设，我将确定使用DAT的障碍和促进因素， 促进艾滋病毒感染者完成3 HP方案。在Aim 2中，我将采用两种低成本DAT来满足用户的需求， 以人为本的设计方法。最后，在目标3中，我将进行试点试验，以评估初步的 在启动3 HP的艾滋病毒感染者中，每种经调整的DAT的有效性和实施情况。结果将提供 NIH R 01申请所需的初步数据，该申请提出了一项随机试验，以评估 一个或两个情境适应DAT的有效性、实施和成本效益，以支持 艾滋病毒感染者完成短期结核病预防治疗。 建议的研究目标直接映射到我的培训目标，包括设计实施 使用混合方法研究的干预措施（目标1和2），利用人类的能力定制实施干预措施 中心设计（目标2）和评估实施干预措施（目标3）。严格执行 以科学为重点的培训加上跨学科的导师团队致力于我的成功将 催化我走向我的职业目标，成为一个独立的物理学家，科学家专注于改善 采取循证干预措施，减少艾滋病毒感染者的结核病负担。

Project Summary/Abstract Tuberculosis (TB) is the leading cause of death among people living with HIV (PLHIV), responsible for over one-third of all HIV deaths worldwide. Tuberculosis preventive therapy (TPT), which can reduce TB incidence by 30-50%, is recommended for all PLHIV by the World Health Organization (WHO). Although a new 12-dose, once-weekly regimen of isoniazid and rifapentine (3HP) via directly observed therapy (DOT) is now available and recommended, treatment completion remains a concern. Additionally, DOT is not a feasible strategy for increasing TB preventive therapy uptake in high burden, low-income settings. To realize the promising potential of 3HP to reduce TB mortality among PLHIV, there is an urgent need for studies that evaluate approaches to support treatment completion with self-administered therapy. The overall objective of this proposal is to determine whether low-cost digital adherence technologies (DATs) can be used to monitor and support completion of 3HP among PLHIV. Our central hypothesis is that a theory- informed adaptation of DATs to fit users' needs will result in high levels of DAT adoption and implementation fidelity. This hypothesis is based on preliminary data from my work in using human-centered design (HCD) methods to adapt a DAT platform to address the adherence challenges faced by patients with active TB. In my mentor's stepped wedge randomized trial, this adapted DAT platform had high levels of acceptability for patients and providers, and improved completion of treatment for active TB. The proposed studies will build upon this prior work to support the use of DATs for scaling-up TB preventive therapy to a key high-risk population. To test this hypothesis in Aim 1 I will identify barriers and facilitators to the use of DATs for facilitating 3HP completion among PLHIV. In Aim 2 I will then adapt two low-cost DATs to fit users' needs using the human centered design methodology. Last, in Aim 3, I will conduct pilot trials to assess the preliminary effectiveness and implementation of each adapted DAT among PLHIV initiating 3HP. The results will provide the preliminary data needed for an NIH R01 application proposing a randomized trial to evaluate the effectiveness, implementation, and cost-effectiveness of one or both contextually adapted DATs for supporting completion of short-course TB preventive therapy among PLHIV. The proposed research aims map directly onto my training objectives including designing implementation interventions using mixed methods research (Aims 1 & 2), tailoring implementation interventions using human- centered design (Aim 2), and evaluating implementation interventions (Aim 3). Rigorous implementation science-focused training coupled with an interdisciplinary mentorship team committed to my success will catalyze me towards my career goal to become an independent physician-scientist focused on improving uptake of evidence-based interventions to reduce TB burden among PLHIV.