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

对移动医疗和传统依从性支持干预措施进行适应性评估，以优化南非耐药结核病和艾滋病毒新治疗方案的结果

• 批准号: 10589840
• 负责人: Max O'Donnell
• 金额: $ 58.37万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-10 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10589840
• 关键词: Adherence; Adverse effects; Adverse event; Antimycobacterial Agents; Behavioral; Behavioral Mechanisms; Behavioral Model; Biological; Caring; Cessation of life; Clinical; Complement; Complex; Cost Effectiveness Analysis; Data; Dose; Drug Interactions; Drug resistance; Drug resistance in tuberculosis; Effectiveness; Effectiveness of Interventions; Electronics; Enrollment; Epidemic; Evaluation; Goals; HIV; HIV/AIDS; HIV/TB; Health; Health Status; Health system; Individual; Integrase; Intervention; Interview; Knowledge; Lamivudine; Measurement; Measures; Mediating; Medical; Methods; Modality; Modeling; Modification; Monitor; Motivation; National Institute of Allergy and Infectious Disease; Oral; Outcome; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Population; Predictive Factor; Psychosocial Assessment and Care; Public Health; Qualitative Methods; Randomized; Recommendation; Regimen; Research; Research Design; Research Priority; Resistance; Social Behavior; South Africa; South African; Southern Africa; Subgroup; Tenofovir; Time; Treatment Failure; Treatment Protocols; Treatment outcome; Tuberculosis; Viral Load result; World Health Organization; antiretroviral therapy; arm; clinical research site; co-infection; community based care; community transmission; effectiveness evaluation; evidence base; experience; high risk; implementation science; implementation trial; improved; inhibitor; innovation; intervention effect; mHealth; medication compliance; mobile computing; mortality; novel; novel therapeutics; patient oriented; person centered; pill; prevent; primary outcome; prospective; psychosocial; randomized trial; service delivery; skills; social; social stigma; standard of care; structural determinants; transmission process; treatment arm; treatment center; trial design; tuberculosis drugs; tuberculosis treatment

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.

项目摘要/摘要 结核病（TB）是艾滋病毒患者死亡的主要原因，导致其中一个 全球三人死亡。在南部非洲，结核病与艾滋病毒流行病之间的互动已导致 为了增加抗药性结核病（DR-TB）的传播，严重破坏了结核病和HIV- 相关的治疗目标。 Bedaquiline（BDQ）是40多年来的第一个新的结核病药物， 世界卫生组织建议将BDQ纳入DR-TB治疗中，以便 更有效，完全完全口服DR-TB治疗。尽管有挑战，但南非的BDQ推出 在降低结核病相关年道形性和提高治疗率方面一直非常成功。 dolutegravir是一种整合酶链转移抑制剂，作为每天一次组合的一部分配制 抗逆转录病毒疗法（ART）在南非公共卫生系统中新近可用。 Tenofovir/Lamivudine/dolutegravir（TLD）优于较旧的比较方案，保护性 由于不良事件而导致的中断，并且与BDQ的相互作用最少。 TLD和BDQ的可用性从根本上改变了DR-TB的治疗范例 艾滋病毒，但需要双重依从性支持才能实现新的好处 患者的治疗疗法，以防止紧急抗性。以患者为中心的依从性 使用社会心理支持和MHealth的支持策略（Mobile支持的健康实践 技术方法可以改善TB DR HIV的结果。 拟议的研究的目的是评估综合干预措施以提高依从性 到BDQ和TLD。使用贝叶斯，自适应随机试验设计，该项目将有效 评估社会心理支持和细胞支持的MHealth的相对贡献 结合和分别依从性支持，以改善临床和生物学结果 用于艾滋病毒和结核病。使用启用细胞的电子药盒测量的BDQ依从性将允许 我们确定与结核病培养转换相关的最佳依从性阈值。我们将 使用基于模型的方法来表征社会行为的行动机制 不同的干预组（包括潜在的无响应）和可修改的因素 障碍和促进者遵守。我们还将评估DR-TB HIV相交的效果 粘附的污名。定性方法将允许对患者进行纵向描述 - 中心处理途径。 完成后，这项研究将满足南非卫生系统的表达需求 用于基于证据的DR-TB HIV依从性干预措施并贡献可推广的知识 关于医学复杂患者的依从性支持方式的相对贡献。