Hybrid trial for Alcohol reduction among people with TB and HIV in India (HATHI)

全球结核病（TB）发病率最高的国家是印度，占所有新发病例的27% 全球约有86，000名艾滋病毒感染者（PWH）。不健康的酒精使用会使 结核病在一般人群中，增加了对原发感染和再激活的易感性，还导致 不良结核病结局，包括治疗依从性下降、治疗失败、违约和死亡。之间 不健康的酒精使用与抗逆转录病毒治疗的使用和依从性减少有关 (ART)降低病毒抑制和增加死亡率。我们在印度的工作表明， 结核病患者中不健康的酒精使用的流行，但它也是结核病的主要原因之一， 治疗违约、失败和死亡率。随着不健康饮酒的高流行率及其与 在低收入和中等收入国家（LMIC），结核病和艾滋病毒治疗结果不利， 测试可扩展的，文化相关的，基于证据的酒精干预措施，并衡量实施因素， 促进更迅速地将有效的干预措施纳入结核病和艾滋病毒/结核病护理。为此，我们建议 HATHI（印度结核病和艾滋病毒感染者减少酒精的混合试验）。这个双臂混合型1型 有效性实施RCT将检查CAP（酒精问题咨询）的有效性， 四节结合认知行为疗法/动机增强疗法减少酒精 与常规护理相比，将干预措施纳入艾滋病毒/结核病和结核病护理（提供者建议， 根据需要治疗）。TB（n=225）和HIV/TB合并感染（n = 225）以及不健康的患者（n=450） 酒精使用将从结核病和艾滋病诊所在2个大型，完善的研究和护理中心， 印度，马哈拉施特拉邦，浦那。在3、6和12个月时测量的有效性结局包括：1）自我报告 酒精使用和磷脂酰乙醇（PEth），一种酒精生物标志物，以及2）TB和HIV临床结局 包括结核病和艾滋病药物治疗依从性、艾滋病病毒抑制、结核病痰/培养转化和 结核病治疗失败、违约或死亡的复合结局。使用RE-AIM实现框架，我们 将使用混合方法评估结核病和艾滋病毒/结核病酒精治疗整合的障碍和促进因素 临床环境和这种干预策略的增量成本。这种混合效率- 实施研究解决了结核病患者不健康饮酒的巨大负担， 印度的结核病/艾滋病毒，结核病负担最高的国家，艾滋病毒负担第三高的国家， 酒精使用是不利治疗结果的重要因素。我们的多学科团队 流行病学家、临床医生、卫生经济学家和行为科学家在以下方面有着成功的记录： 在美国和印度进行临床试验和酒精干预。我们的研究将提供急需的 为地方和全球政策提供信息的证据，并改善受艾滋病毒、结核病和其他疾病影响最严重的人的治疗结果 不健康的饮酒

The highest incidence of tuberculosis disease (TB) in the world is in India, accounting for 27% of all new cases globally, with approximately 86,000 among persons with HIV (PWH). Unhealthy alcohol use triples the risk of TB in the general population, increasing susceptibility to primary infection and reactivation, and also leads to poor TB outcomes including decreased treatment adherence, treatment failure, default and death. Among PWH, unhealthy alcohol use is associated with decreased use of and adherence to antiretroviral therapy (ART), lower viral suppression and increased mortality. Our work in India demonstrates not only high prevalence of unhealthy alcohol use among patients with TB, but also that it is one of the major reasons for treatment default, failure, and mortality. With the high prevalence of unhealthy alcohol use and its association with adverse TB and HIV treatment outcomes in low and middle income countries (LMIC), it is imperative to test scalable, culturally relevant, evidence-based alcohol interventions and measure implementation factors to facilitate more rapid integration of effective interventions into TB and HIV/TB care. To this end, we propose HATHI (Hybrid trial for Alcohol reduction among people with TB and HIV in India). This 2-arm hybrid type 1 effectiveness-implementation RCT will examine the effectiveness of CAP (Counseling on Alcohol Problems), a four-session combined Cognitive Behavioral Therapy/Motivational Enhancement Therapy alcohol reduction intervention integrated into HIV/TB and TB care, compared with usual care (provider advice, referral to treatment as needed). Patients (n=450) with TB (n=225) and HIV/TB co-infection (n=225) and unhealthy alcohol use will be recruited from TB and HIV clinics at 2 large, well-established research and care centers in Pune, Maharashtra India. Effectiveness outcomes measured at 3, 6 and 12 months include 1) self-reported alcohol use and phosphatidyl ethanol (PEth), an alcohol biomarker, and 2) TB and HIV clinical outcomes including TB and HIV medication adherence, HIV viral suppression, TB sputum/culture conversion and the composite outcome of TB treatment failure, default or death. Using the RE-AIM implementation framework, we will use mixed methods to assess barriers and facilitators to alcohol treatment integration in TB and HIV/TB clinical settings and the incremental costs of this intervention strategy. This hybrid effectiveness- implementation study addresses the huge burden of unhealthy alcohol use among persons with TB and TB/HIV in India, the country with the highest burden of TB, 3rd highest burden of HIV, and where unhealthy alcohol use is a significant contributor to unfavorable treatment outcomes. Our multidisciplinary team of epidemiologists, clinicians, health economists and behavioral scientists has a successful track record for conducting clinical trials and alcohol interventions in the US and India. Our research will provide much-needed evidence to inform local and global policy, and improve outcomes for persons most affected by HIV, TB, and unhealthy alcohol use.