Adaptive evaluation of mHealth and conventional adherence support interventions to optimize outcomes with new treatment regimens for drug-resistant tuberculosis and HIV in South Africa

项目摘要/摘要 结核病是艾滋病毒携带者死亡的主要原因，每1人中就有1人死于结核病。 全球范围内有三人死亡。在南部非洲，结核病和艾滋病毒流行之间的相互作用导致 耐药结核病(DR-TB)传播增加，严重破坏结核病和艾滋病毒- 相关治疗目标。贝达奎林(BDQ)是40多年来第一种治疗结核病的新药， 世界卫生组织建议将BDQ纳入DR-TB治疗，允许 更有效的、完全口服的DR-TB治疗。尽管面临挑战，BDQ在南非推出 在降低结核病相关死亡率和提高治愈率方面取得了巨大成功。 多洛替格列韦，一种整合酶链转移抑制剂，作为每日一次联合治疗的一部分 抗逆转录病毒疗法(ART)是南非公共卫生系统新推出的一种疗法。 替诺福韦/拉米夫定/多洛替格韦(TLD)优于旧的比较方案，保护 因不良事件而停用，与BDQ的交互作用最小。 TLD和BDQ的问世从根本上改变了DR-TB的治疗模式 但需要在双重坚持支持方面取得进展，才能实现新的 为患者提供治疗，并防止出现紧急耐药性。以患者为中心的坚持 使用心理社会支持和移动健康的支持战略(由移动设备支持的健康实践 技术)的方法可能会改善耐药结核病艾滋病毒的结果。 这项拟议研究的目标是评估提高依从性的综合干预措施 致BDQ和TLD。使用贝叶斯、自适应随机试验设计，该项目将有效 评估心理社会支持和手机支持的移动健康的相对贡献 联合和单独提供坚持支持，以改善临床和生物学结果 治疗艾滋病毒和结核病。使用蜂窝启用的电子药盒测量的BDQ依从性，将允许 美国确定与结核病培养转化相关的最佳依从性阈值。我们会 使用基于模型的方法来描述 不同的干预武器(包括潜在的无反应)，以及存在的可修改因素 遵守的障碍和促进者。我们还将评估DR-TB HIV交叉感染的效果 粘着的污点。定性方法将允许对患者的纵向描述- 以治疗路径为中心。 一旦完成，这项研究将满足南非卫生系统明确的需求 用于循证的DR-TB HIV依从性干预，并提供概括性知识 关于依从性支持方式在复杂医学患者中的相对贡献。

Project Summary/Abstract Tuberculosis (TB) is the leading cause of mortality among people living with HIV, causing one in three deaths world-wide. In southern Africa, interaction between TB and HIV epidemics has led to increased transmission of drug-resistant TB (DR-TB), critically undermining both TB and HIV- related treatment targets. Bedaquiline (BDQ) is the first new TB drug in over 40 years, and the World Health Organization recommends the inclusion of BDQ in DR-TB treatment allowing for more effective, entirely oral DR-TB treatment. Despite challenges, BDQ rollout in South Africa has been highly successful in reducing TB associated-mortality and improving cure rates. Dolutegravir, an integrase strand transfer inhibitor, formulated as part of a once-daily combination antiretroviral therapy (ART), is newly available in the South African public health system. Tenofovir/lamivudine/dolutegravir (TLD) is superior to older comparator regimens, protective for discontinuation due to adverse events, and has minimal interaction with BDQ. The availability of TLD and BDQ has radically transformed the treatment paradigm for DR-TB HIV but advances in dual adherence support are needed to realize the benefits of new therapeutics for patients, and to prevent emergent resistance. Patient-centered adherence support strategies using psychosocial support and mHealth (health practices supported by mobile technologies) approaches may improve DR-TB HIV outcomes. The goal of the proposed study is to evaluate an integrated intervention to enhance adherence to BDQ and TLD. Using a Bayesian, adaptive randomized trial design, this project will efficiently evaluate the relative contribution of psychosocial support and cellular-supported mHealth adherence support, in combination and separately, to improve clinical and biological outcomes for HIV and TB. BDQ adherence measured using cellular-enabled electronic pill boxes, will allow us to determine optimal adherence thresholds associated with TB culture conversion. We will use a model-based approach to characterize socio-behavioral mechanisms of action for the different intervention arms (including potential non-response), and modifiable factors that present barriers and facilitators to adherence. We will also evaluate the effect of DR-TB HIV intersectional stigma on adherence. Qualitative methods will allow for longitudinal description of patient- centered treatment pathways. Once completed, this study will meet the expressed need of the South African health system for evidence-based DR-TB HIV adherence interventions and contribute generalizable knowledge about the relative contributions of adherence support modalities in medically complex patients.