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

提供短期结核病预防治疗的选项：3HP 选项试验

基本信息

批准号：
9753350
负责人：
Adithya Cattamanchi
金额：
$ 61.41万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9753350
关键词：
Address Adherence Adopted Adverse event Africa South of the Sahara African Caring Cause of Death Clinic Clinic Visits Communication Counseling Country Data Decision Aid Directly Observed Therapy Disadvantaged Dose Economic Models Effectiveness Enrollment Evaluation Failure HIV HIV/TB Health Health Personnel Health system Hybrids Immunosuppression Incidence Intervention Interview Lead Life Low income Methods Modeling Motivation Patients Pharmaceutical Preparations Policies Population Prevention Preventive therapy Process Randomized Recommendation Regimen Research Infrastructure Safety Savings Self Administration Services Standardization Structure Syndrome Testing Theoretical model Toxic effect Treatment Protocols Trust Tuberculosis Uganda United States National Institutes of Health Visit Work arm barrier to care base behavior change comparative comparative effectiveness contextual factors cost cost effective cost effectiveness design disability-adjusted life years improved innovation isoniazid mHealth mortality novel patient engagement patient oriented patient-level barriers pill preference prevent primary outcome programs randomized trial relative cost rifapentine scale up secondary outcome shared decision making theories therapy duration tool treatment adherence tuberculosis treatment uptake

项目摘要

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.

项目摘要众所周知，异烟肼预防疗法（IPT）可减少艾滋病毒患者的结核病（TB）（PLHIV）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PLHIV很少已经收到了IPT。已经解决了许多历史障碍至IPT扩大规模的障碍，但仍然存在关键障碍，包括长期治疗持续时间（6-9个月），高药伯嫩（180-270剂）以及对毒性的担忧。在大多数情况下，不到一半的PLHIV启动IPT完成了整个课程。一个新的12剂，每周一次最近的Isoniazid和利福丁疗法（3HP）的疗法被证明具有相似的效率，更高的完成率，相对于IPT的九个月，更好的安全性。但是要实现利用和影响，必须以在撒哈拉以南非洲为PLHIV工作的方式实施3HP。该提案的总体目的是确定以患者为中心的分娩策略，该策略将有助于3HP PLHIV在撒哈拉以南非洲的吸收。 3HP可以由医疗工作者（DOT）直接观察到自我管理（SAT）；这两个选项都有相对优势和缺点。因此，我们建议专注于共享决策作为优化3HP接受和完成的方法。我们的中心假设是，在理论知识的点和SAT策略之间提供PLHIV是一个明智的选择优化以克服依从性的关键障碍将导致更大的3HP启动和完成。在AIM 1中，我们将通过在乌干达坎帕拉的1656年PLHIV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的接受和完成：1）促进点； 2）便利的星期六； 3）准备的点和准备好的SAT之间的患者选择（使用决策辅助）。这些干预措施是专门设计的，以克服使用新理论的患者级别遵守障碍行为改变模型（COM-B）。 DOT和SAT的便利将包括标准化咨询，简化了诊所就诊，与访问相关的费用的报销以及基于SMS的沟通。次要结果包括3HP治疗后一年的广告活动和结核病事件。在AIM 2中，我们将员工一种评估每个交付策略核心组件的实施的混合方法方法，以及他们是否修改了目标障碍。最后，在AIM 3中，我们将执行每个的经验成本战略和构建经济模型，以比较3HP交付的成本和成本效益彼此相关的策略，没有预防疗法和IPT。 3HP - 预防结核病的最有承诺的干预措施 - 除非可以交付有效，以患者为中心的方式。我们提议的研究员工共享的创新方法通过一种新型方案进行决策，以提供挽救生命的干预措施（TB预防疗法）迄今为止采用不佳。该试验将通过提供全面评估来解决NIH和全球优先事项需要在高压荷兰非洲环境中有关PLHIV的3HP规模的政策。