The Role of Alcohol Use in Incident TB Infection and Active TB Disease Among Persons Living with HIV

饮酒在艾滋病毒感染者结核感染和活动性结核病中的作用

基本信息

批准号：
10303986
负责人：
JUDITH ALISSA HAHN
金额：
$ 52.29万
依托单位：
BOSTON MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-10 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10303986
关键词：
AIDS/HIV problem Adherence Adult Africa South of the Sahara Age Alcohol consumption Alcohols Behavior Therapy Biological Markers Body mass index Boston CD4 Positive T Lymphocytes Cause of Death Cell Count Collaborations Country Crowding Cutaneous Tuberculosis Disease Enrollment Exposure to Future Gender Goals HIV HIV/TB Heavy Drinking Household Hypersensitivity skin testing Immunity Incidence International Intervention Knowledge Measurement Mediator of activation protein Morbidity - disease rate Mycobacterium tuberculosis Odds Ratio Participant Pathway interactions Persons Phase Policies Population Positioning Attribute Preventive therapy Prospective Studies Research Risk Risk Estimate Role Russia Sampling Smoking Socioeconomic Status Test Result Testing Time Treatment outcome Tuberculin Test Tuberculosis Uganda Viral alcohol intervention alcohol measurement alcohol research alcohol risk antiretroviral therapy base cigarette smoking cofactor cohort drinking environmental tobacco smoke environmental tobacco smoke exposure follow-up high risk high risk drinking high risk population low socioeconomic status mortality phosphatidylethanol prevent programs prospective reduced alcohol use scale up screening therapy adherence tuberculosis treatment

项目摘要

Tuberculosis (TB) is the leading cause of death among persons living with HIV (PLWH); TB disease rates for PLWH engaging in heavy alcohol use are 2-3 times those of alcohol abstainers and TB treatment outcomes are poorer. TB preventive therapy (TPT) reduces the risk of progression from latent TB infection (LTBI) to TB disease, and is being scaled up for PLWH in many high HIV/TB incidence settings. However, TPT does not prevent new or repeat TB infection after TPT has ended, therefore PLWH who engage in heavy alcohol use may be at increased risk for acquiring new TB infection even after receiving TPT. There has been little research examining the impact of alcohol use on acquiring new TB infection separately from progressing to active TB disease; this limits our ability to understand the role of alcohol use on the separate phases of TB to optimize intervention strategies most appropriate for each. We propose to examine the risk of acquiring TB infection and of incident active TB disease among PLWH with heavy alcohol use after receipt of TPT in PLWH in Uganda, a high HIV/TB country. Our goal is to inform interventions to reduce the risk for acquiring new TB infection in this group, including behavioral interventions to reduce alcohol use, and TPT strategies, such as repeat short-course TPT to prevent active TB disease. First, we propose to examine the acquisition of new TB infection by level of alcohol use among a cohort of PLWH with prior negative tuberculin skin test (TST) results, in a sample of PLWH enriched for heavy alcohol use (Aim 1). We will adjust for key confounders such as cigarette smoking, second-hand smoke, socio-economic status, household crowding, gender, age, nadir CD4+ T cell count, and prior TPT receipt. We will also examine the mediators of alcohol use on risk of TB infection, such as lack of HIV viral suppression, bar attendance, and low body mass index, to determine if existing alcohol interventions should incorporate these as additional targets. To accomplish this aim, we will leverage a large cohort of PLWH including 50% engaging in high-risk drinking, that we previously tested for LTBI from 2017 to 2020 who were TST negative. We will re-enroll 500 persons and conduct repeat TST and active TB screening yearly, over 4 years, to determine the rate of acquiring new TB infection. We will also determine whether PLWH who engage in heavy alcohol use and have LTBI are at increased risk of progressing to active TB disease, despite receipt of TPT, compared to persons engaging in lower risk or no alcohol use (Aim 2). For Aim 2, we will leverage our prior cohort of 990 PLWH with LTBI who received TPT, with over 5000 person- years of follow-up and well-characterized alcohol use and TPT electronic adherence measurement. Both aims will leverage cohorts uniquely suited for these analyses and use objective alcohol biomarkers. These studies will provide unprecedented prospective evidence needed to effectively target alcohol reduction interventions and inform TPT strategies—such as repeated short courses of TPT—to prevent new TB infection and reduce the risk of progression to TB disease for a high-risk group of PLWH: those engaging in heavy alcohol use.

结核病（TB）是艾滋病毒（PLWH）患者中死亡的主要原因；结核病病率大量饮酒的PLWH是酒精和结核病治疗结果的2-3倍贫穷。结核病预防疗法（TPT）降低了从潜在结核病感染（LTBI）发展为结核病的风险疾病，正在许多高HIV/TB事件设置中为PLWH缩放。但是，TPT没有 TPT结束后，请防止新的或重复的结核病感染，因此可以从事大量酒精即使在收到TPT后，也可能会增加获得新结核病感染的风险。几乎没有研究研究饮酒对获得新结核病感染的影响分别从进展到活性结核病；这限制了我们了解酒精使用在结核病单独阶段的作用的能力优化最适合每种干预策略。我们建议检查获取结核病的风险在PLWH中收到TPT后，PLWH中的感染和事件活跃的TB疾病在PLWH中使用大量使用在乌干达，一个高艾滋病毒/结核病国家。我们的目标是告知干预措施，以减少获得新结核病的风险该组的感染，包括减少酒精使用的行为干预措施，以及TPT策略，例如重复短期TPT，以防止活跃的结核病疾病。首先，我们建议检查新结核病的获取通过饮酒水平感染的PLWH队列与先前的结核蛋白皮肤测试（TST）结果，结果在富含大量酒精的PLWH样品中（AIM 1）。我们将调整关键混杂因素，例如吸烟，二手烟，社会经济地位，家庭拥挤，性别，年龄，Nadir CD4+ T细胞计数和先前的TPT收据。我们还将检查饮酒的介体在结核病感染的风险中，例如缺乏艾滋病毒病毒抑制，律师的出勤率和低体重指数，以确定是否存在酒精干预措施应将其纳入其他目标。为了实现这一目标，我们将利用大量的PLWH队列，包括50％从事高风险饮酒，我们以前从中测试过LTBI 2017年至2020年是负面的。我们将重新注册500人，并进行重复的TST和Active TB 每年筛查4年以上，以确定获得新结核病感染的速度。我们还将确定是否从事大量酒精饮酒并让LTBI的PLWH有升级的风险与从事较低风险或不使用酒精的人相比，结核病疾病，目的地收到了TPT（AIM 2）。为了 AIM 2，我们将利用我们先前与收到TPT的LTBI的990 PLWH的队列，并拥有超过5000人 - 多年的随访和良好的酒精使用和TPT电子依从性测量。两个目标将利用非常适合这些分析的人群并使用客观的酒精生物标志物。这些研究将提供有效针对饮酒干预措施的前所未有的前瞻性证据并告知TPT策略（例如重复的TPT），以防止新的结核病感染并减少高风险的PLWH的进展风险：从事大量饮酒的人。