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

项目总结 已知异烟肼预防疗法(Ipt)可降低艾滋病毒携带者中的结核病(TB)发病率。 (PLHIV)，并被认为是国家艾滋病计划的核心服务。然而，撒哈拉以南非洲的艾滋病病毒感染者寥寥无几 已经收到了IPT。IPT扩大的许多历史障碍正在解决，但关键障碍仍然存在， 包括疗程长(6-9个月)、高药量负担(180-270剂)和对毒性的担忧。 在大多数情况下，只有不到一半的艾滋病毒感染者完成了整个课程。新的12剂，每周一次 异烟肼和利福喷丁(3HP)方案最近被证明具有类似的疗效，更高的完成率， 与9个月的IPT相比，安全状况更好。但要实现利用率和影响，必须 以适用于撒哈拉以南非洲艾滋病病毒感染者的方式实施3HP。 这项建议的总体目标是确定以患者为中心的交付策略，以促进3HP 撒哈拉以南非洲艾滋病毒感染者的感染情况。3HP可由医护人员直接观察(DOT)或 自我管理(SAT)；两种选择都有相对的优势和劣势。因此，我们建议 将共享决策作为优化3HP验收和完工的一种方法。我们的中央 假设是为PLHIV提供了一个在理论知情的DOT和SAT策略之间的明智选择 经过优化以克服遵守的关键障碍，将导致更多的3HP启动和完成。 在目标1中，我们将通过在乌干达坎帕拉的1656名艾滋病毒感染者中进行随机试验来检验我们的假设， 使用以下交付策略比较3HP的接受度和完成情况：1)促进DOT；2) 易化SAT；以及3)患者在易化DOT和易化SAT之间的选择(使用决策辅助)。这些 干预措施是专门为克服患者层面的坚持障碍而设计的，使用了一种新的理论 行为改变模型(COM-B)。DOT和SAT的便利化将包括标准化咨询， 简化了诊所就诊、与就诊相关的费用报销以及基于短信的通信。次要的 结果包括3HP治疗后一年内的不良事件和结核病发病率。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实施情况， 以及他们是否修改了目标壁垒。最后，在目标3中，我们将对每个目标进行经验成本计算 制定战略并构建经济模型，以比较3HP交付的成本和成本效益 策略相对，无预防性治疗和IPT。 3HP--最有希望的结核病预防干预措施--除非能够交付，否则不会扩大规模 有效并以患者为中心的方式。我们建议的研究采用了一种创新的共享方法 使用一种新的方案进行决策，以提供挽救生命的干预措施(结核病预防疗法)，该疗法已被 到目前为止还没有得到很好的采纳。这项试验将通过提供综合评估来解决NIH和全球优先事项 需要告知有关在结核病负担高的非洲环境中扩大艾滋病毒/艾滋病之间的3HP规模的政策。

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.