Options for Delivery of Short-Course Tuberculosis Preventive Therapy: The 3HP Options Trial

项目摘要 众所周知，异烟肼预防性治疗（IPT）可降低艾滋病毒感染者的结核病（TB）发病率 艾滋病毒感染者（PLHIV），并被认为是国家艾滋病方案的核心服务。然而，在撒哈拉以南非洲， 我收到了IPT。扩大IPT的许多历史障碍正在得到解决，但关键障碍仍然存在， 包括治疗持续时间长（6-9个月）、高药丸负担（180-270剂）和对毒性的担忧。 在大多数情况下，开始IPT的艾滋病毒感染者中只有不到一半完成了整个课程。新的12剂，每周一次 异烟肼和利福喷丁（3 HP）的方案最近显示具有相似的功效，更高的完成率， 并且相对于九个月的IPT来说安全性更好。但要实现利用率和影响力， 在撒哈拉以南非洲地区，以一种对艾滋病毒感染者有效的方式实施3 HP。 本提案的总体目标是确定一个以患者为中心的交付策略，以促进3 HP 艾滋病毒感染者在撒哈拉以南非洲的感染情况。3 HP可以由医护人员（DOT）直接观察， 自我管理（SAT）;两种选择都有相对的优点和缺点。因此我们建议 注重共同决策，作为优化3 HP验收和完成的一种方法。我们的中央 假设是，提供PLHIV知情选择之间的理论知情DOT和SAT策略 经过优化以克服遵守的关键障碍，将导致更多的3 HP启动和完成。 在目标1中，我们将在乌干达的坎帕拉对1656名艾滋病毒感染者进行随机试验， 使用以下交付策略比较3 HP的验收和完成情况：1）促进DOT; 2） 促进SAT;和3）患者选择（使用决策援助）之间的促进DOT和促进SAT。这些 干预措施是专门设计的，以克服患者层面的障碍，坚持使用新的理论， 行为改变模型（COM-B）。DOT和SAT的促进将包括标准化的咨询， 简化诊所就诊、报销就诊相关费用以及基于短信的通信。二次 结果包括3 HP治疗后一年内的不良事件和TB发病率。在目标2中，我们将 采用混合方法评估每项交付战略核心组成部分的执行情况， 以及它们是否改变了目标屏障。最后，在目标3中，我们将对每一个项目进行经验成本计算。 战略和构建经济模型，以比较3 HP交付的成本和成本效益 没有预防性治疗和IPT。 3 HP--最有希望的结核病预防干预措施--将不会扩大规模，除非能够提供 以病人为中心的方式。我们提出的研究采用了一种创新的方法， 决策与一种新的方案，提供挽救生命的干预措施（结核病预防性治疗）， 到目前为止还没有被采纳。这项试验将通过提供全面的评估来解决NIH和全球优先事项 需要为在结核病负担高的非洲环境中艾滋病毒感染者中扩大3 HP规模的政策提供信息。

PROJECT SUMMARY Isoniazid preventive therapy (IPT) is known to reduce tuberculosis (TB) incidence among people living with HIV (PLHIV) and is considered a core service of National AIDS Programs. Yet, few PLHIV in sub-Saharan Africa have received IPT. Many historical roadblocks to IPT scale-up are being addressed, but critical barriers remain, including the long duration of therapy (6-9 months), high pill burden (180-270 doses) and concerns about toxicity. In most settings, less than half of PLHIV initiating IPT complete the full course. A new 12-dose, once-weekly regimen of isoniazid and rifapentine (3HP) was recently shown to have similar efficacy, higher completion rates, and a better safety profile relative to nine months of IPT. But to achieve utilization and impact, it is essential to implement 3HP in a fashion that works for PLHIV in sub-Saharan Africa. The overall objective of this proposal is to identify a patient-centered delivery strategy that will facilitate 3HP uptake by PLHIV in sub-Saharan Africa. 3HP can either be directly observed by a healthcare worker (DOT) or self-administered (SAT); both options have relative advantages and disadvantages. We therefore propose to focus on shared decision-making as a method to optimize 3HP acceptance and completion. Our central hypothesis is that offering PLHIV an informed choice between theory-informed DOT and SAT strategies optimized to overcome key barriers to adherence will result in greater 3HP initiation and completion. In Aim 1, we will test our hypothesis by conducting a randomized trial among 1656 PLHIV in Kampala, Uganda, to compare acceptance and completion of 3HP using the following delivery strategies: 1) Facilitated DOT; 2) Facilitated SAT; and 3) Patient choice (using a decision aid) between facilitated DOT and facilitated SAT. These interventions were specifically designed to overcome patient-level barriers to adherence using a new theoretical model of behavior change (COM-B). Facilitation of both DOT and SAT will include standardized counseling, streamlined clinic visits, reimbursement of visit-related costs, and SMS-based communication. Secondary outcomes include adverse events and TB incidence over one year following 3HP treatment. In Aim 2, we will employ a mixed methods approach to assess the implementation of core components of each delivery strategy, and whether or not they modified targeted barriers. Last, in Aim 3, we will perform empiric costing of each strategy and construct economic models to compare the costs and cost-effectiveness of the 3HP delivery strategies relative to each other, no preventive therapy and IPT. 3HP – the most promising intervention for TB prevention – will not be scaled up unless it can be delivered effectively and in a patient-centered fashion. Our proposed study employs an innovative approach of shared decision-making with a novel regimen to deliver a life-saving intervention (TB preventive therapy) that has been poorly adopted to date. This trial will address NIH and global priorities by providing the comprehensive evaluation needed to inform policy regarding 3HP scale-up among PLHIV in high TB-burden African settings.