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

项目概要/摘要 结核病是艾滋病毒感染者死亡的主要原因， 全世界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）的传播增加，严重破坏结核病和艾滋病毒- 相关治疗目标。贝达喹啉（BDQ）是40多年来第一种新的结核病药物， 世界卫生组织建议将BDQ纳入耐药结核病治疗， 更有效的完全口服耐药结核病治疗。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非常成功。 Dolutegravir，一种整合酶链转移抑制剂，作为每日一次复方制剂的一部分 抗逆转录病毒疗法（ART）是南非公共卫生系统新近提供的。 替诺福韦/拉米夫定/度鲁特韦（Tenofovir/lamivudine/dolutegravir）上级旧的比较方案， 由于不良事件而停药，与BDQ的相互作用极小。 抗结核药物和BDQ的可用性从根本上改变了耐药结核病的治疗模式 艾滋病毒，但需要在双重坚持支持方面取得进展，以实现新疗法的好处 治疗患者，并防止出现耐药性。以患者为中心的依从性 使用心理社会支持和移动健康（由移动的支持的健康实践）的支持战略 技术）方法可能会改善耐药结核病艾滋病毒的结果。 这项研究的目的是评估一种综合干预措施，以提高依从性 到BDQ和BDD。使用贝叶斯，适应性随机试验设计，该项目将有效地 评估心理社会支持和手机支持的移动健康的相对贡献 联合或单独提供依从性支持，以改善临床和生物学结局 艾滋病和结核病的治疗使用蜂窝式电子药盒测量的BDQ依从性将允许 确定与结核菌培养转化相关的最佳依从性阈值。我们将 使用基于模型的方法来描述社会行为的行动机制， 不同的干预组（包括潜在的无应答），以及存在的可改变因素 阻碍和促进因素。我们还将评估耐药结核病和艾滋病毒交叉感染的影响， 坚持的耻辱。定性方法将允许对患者进行纵向描述- 中心治疗路径。 这项研究一旦完成，将满足南非卫生系统的明确需求。 支持循证耐药结核病艾滋病毒依从性干预措施，并提供可推广的知识 关于医学复杂患者中依从性支持模式的相对贡献。

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.