The impact of alcohol consumption on TB treatment outcomes

 描述(申请人提供)：结核病仍是全球第二大传染病死亡原因，仅次于艾滋病毒/艾滋病。包括南非在内的许多国家的回溯性研究一直报告说，与不饮酒的患者相比，有问题的饮酒患者除了有更高的结核病负担外，还会有更差的结核病治疗结果，包括延迟培养转换，以及更高的治疗失败、复发和死亡率。据估计，全球有10%的结核病死亡可归因于有问题的酒精使用。尽管导致结核病结果恶化的一个原因是治疗依从性差，但观察性研究和动物模型表明，在对次优依从性进行调整后，饮酒和结核病治疗结果之间的关系仍然存在。一个潜在的生物学机制是通过酒精对结核病药物的药代动力学(PK)和药效学(PD)的影响。有问题的酒精使用可能会导致结核病药物的吸收较差和/或代谢加快，从而增加次优绝育的风险。迫切需要确定导致结核病治疗反应不佳的可改变因素，了解个人和人群一级治疗反应不佳的驱动因素对结核病控制至关重要。波士顿医学中心(BMC)、波士顿大学医学院(BUSM)、南非医学研究委员会(MRC)和开普敦大学(UCT)的研究人员提议进行第一项前瞻性研究，试图澄清问题饮酒对结核病治疗结果有害影响的潜在因果机制。我们计划在南非伍斯特招募438名培养阳性的肺结核病患者，这是一个结核病和酗酒问题高度流行的地区。这项研究的具体目的是：1)检查问题酒精使用与结核病治疗结果之间的关联，以及(Ii)证明这些关联独立于对结核病治疗的坚持而存在，以及2)评估问题酒精使用对结核病药物的PK/PD的影响。我们的多学科方法将提供迄今为止最好的证据，解决结核病和酒精中毒之间的复杂相互作用，并为面临这两种流行病的国家提供管理战略。

 DESCRIPTION (provided by applicant): After HIV/AIDS, tuberculosis (TB) remains the second leading cause of death due to an infectious disease globally. Retrospective studies from many countries, including South Africa, have consistently reported that in addition to having a higher burden of TB disease, patients with problem alcohol use have worse TB treatment outcomes, including delayed culture conversion and higher rates of treatment failure, relapse, and death, compared to patients who do not consume alcohol. An estimated 10% of TB deaths are attributable to problematic alcohol use globally. Although one causal pathway to worse TB outcomes is through poor treatment adherence, observational studies and animals models suggest that the relationship between alcohol use and TB treatment outcomes persists after adjustment for suboptimal adherence. One potential biological mechanism is through alcohol's impact on the pharmacokinetics (PK) and pharmacodynamics (PD) of TB drugs. Problem alcohol use may lead to poorer absorption and/or accelerated metabolism of TB drugs, thereby increasing the risk of suboptimal sterilization. There is an urgent need to identify modifiable factors that contribute to poor TB treatment response, and understanding drivers of poor treatment response, both at the individual and population level, is essential for TB control. Investigators at Boston Medical Center (BMC), Boston University School of Medicine (BUSM), the South African Medical Research Council (MRC), and the University of Cape Town (UCT) propose to conduct the first prospective study to attempt to clarify the causal mechanisms underlying the deleterious effects of problem alcohol use on TB treatment outcomes. We plan to recruit 438 culture positive, pulmonary TB patients in Worcester, South Africa, an area highly endemic for both TB and problem alcohol use. The specific aims of this study are: 1) examine the associations between problem alcohol use and TB treatment outcomes, and (ii) demonstrate that these associations persist independent of adherence to TB treatment, and 2) to evaluate the effect of problematic alcohol use on the PK/PD of TB drugs. Our multidisciplinary approach will provide the best evidence to date addressing the complex interactions between TB and alcoholism and inform management strategies for countries facing these two epidemics.