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

• 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
• 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

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) 是艾滋病毒感染者 (PLWH) 死亡的主要原因；结核病发病率 大量饮酒的感染者和结核病治疗结果是戒酒者的 2-3 倍 比较穷。结核病预防治疗 (TPT) 可降低从潜伏性结核感染 (LTBI) 进展为结核病的风险 疾病，并正在许多艾滋病毒/结核病高发地区扩大针对艾滋病毒/艾滋病感染者的治疗范围。然而，TPT 并不 TPT 结束后预防新的或重复的结核感染，因此对于酗酒的感染者和感染者 即使在接受 TPT 后，感染新结核病的风险也可能增加。已经很少有 研究分别考察了饮酒对新发结核感染和进展为结核病感染的影响 活动性结核病；这限制了我们了解饮酒对结核病各个阶段的作用的能力 优化最适合每个人的干预策略。我们建议检查感染结核病的风险 接受 TPT 后严重饮酒的 PLWH 中的感染和活动性结核病事件 乌干达是艾滋病毒/结核病高发国家。我们的目标是为干预措施提供信息，以降低感染新结核病的风险 该群体的感染情况，包括减少饮酒的行为干预和 TPT 策略，例如 重复短期 TPT 以预防活动性结核病。首先，我们建议审查新TB的收购 先前结核菌素皮肤试验（TST）结果呈阴性的感染者群体中的酒精使用水平的感染情况， 富含酒精的感染者样本（目标 1）。我们将针对关键混杂因素进行调整，例如 吸烟、二手烟、社会经济地位、家庭拥挤、性别、年龄、最低点 CD4+ T 细胞计数和之前的 TPT 接收。我们还将研究饮酒对结核感染风险的影响因素， 例如缺乏 HIV 病毒抑制、酒吧出勤率和低体重指数，以确定是否存在 酒精干预措施应将这些作为额外目标。为了实现这一目标，我们将利用 一大群感染者，其中 50% 从事高风险饮酒，我们之前对他们进行了 LTBI 检测 2017 年至 2020 年 TST 呈阴性的人。我们将重新招募 500 人并进行重复 TST 和活动性结核病 四年内每年进行一次筛查，以确定新感染结核病的比率。我们还将确定 大量饮酒并患有 LTBI 的 PLWH 进展为活跃的风险是否增加 与饮酒风险较低或不饮酒的人相比，尽管接受了 TPT，但仍患有结核病（目标 2）。为了 目标 2，我们将利用之前接受 TPT 的 990 名 LTBI 感染者和 PLWH 队列，其中超过 5000 人- 多年的跟踪和明确的酒精使用情况以及 TPT 电子依从性测量。两个目标 将利用独特适合这些分析的队列并使用客观的酒精生物标志物。这些研究 将提供有效针对减少酒精干预措施所需的前所未有的前瞻性证据 并告知 TPT 策略（例如重复短期 TPT 疗程），以预防新的结核病感染并减少 感染者高危人群（即酗酒者）进展为结核病的风险。