Interventions to reduce alcohol use and increase adherence to TB preventive therapy among HIV/TB co-infected drinkers (DIPT 1/2)

减少饮酒并提高艾滋病毒/结核病合并感染饮酒者对结核病预防治疗依从性的干预措施（DIPT 1/2）

• 批准号: 10238903
• 负责人: JUDITH ALISSA HAHN
• 金额: $ 49.87万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10238903
• 关键词: Address; Adherence; Adult; Africa; Africa South of the Sahara; Alcohol consumption; Alcoholic beverage heavy drinker; Alcohols; Antibiotics; Antitubercular Agents; Behavior; Cause of Death; Cessation of life; Clinic; Clinical; Consumption; Control Groups; Counseling; Country; Data; Disease; Effectiveness; Event; Glucuronides; HIV; HIV/TB; Hair; Heavy Drinking; Hepatotoxicity; Heterogeneity; Hour; Incentives; Incidence; Income; Ingestion; Intervention; Life; Liver; Low income; Measurement; Measures; Mediator of activation protein; Monitor; Morbidity - disease rate; Participant; Patient Self-Report; Pattern; Persons; Pharmaceutical Preparations; Prevalence; Preventive therapy; Prize; Randomized; Regimen; Resources; Rewards; Risk; Safety; Sample Size; Sampling; Savings; System; Testing; Toxic effect; Tuberculosis; Uganda; Urine; Viral; Viral Load result; Visit; alcohol measurement; alcohol use disorder; antiretroviral therapy; arm; base; behavior test; cohort; cost; drinking; economic impact; economic incentive; effectiveness evaluation; high risk; high risk population; improved; incentive strategies; incentive-based intervention; isoniazid; low income country; medication safety; mortality; novel; phosphatidylethanol; pill; point of care; point of care testing; prevent; primary outcome; rapid test; reduced alcohol use; reduced substance use; therapy adherence; treatment arm; virology

ABSTRACT TB is the leading cause of death among persons with HIV worldwide. Globally, approximately 25% of persons with HIV are heavy drinkers, and heavy alcohol use is associated with a 3-fold higher risk of TB disease compared to no alcohol use, thus HIV-infected persons who drink alcohol are at high risk for TB. Six months of isoniazid (INH) preventive therapy (IPT) reduces TB incidence and mortality by 30-50% above the positive impact of antiretroviral therapy (ART). However, INH can be toxic to the liver, and thus many heavy alcohol users in resource-limited settings such as east Africa are not offered IPT. In addition, heavy alcohol users have poorer ART adherence and data suggest decreased IPT adherence as well. Thus interventions are needed to both decrease alcohol use and increase IPT adherence, and thereby reduce INH toxicity, TB morbidity and mortality in this high-risk population. The use of incentives to promote healthy behavior has been shown to be a highly effective approach for reducing substance use and for improving adherence to HIV and TB regimens in high-income countries. Reducing alcohol use may create a window for safe and effective IPT use by decreasing hepatotoxicity and increasing IPT adherence; however, additional interventions for IPT adherence may be needed. The use of incentives conditional on reduced alcohol use or increased INH adherence in resource-limited settings has been previously limited by the lack of reliable, rapid tests for these behaviors. Recent technological advances allow for point of care (POC) urine testing for recent alcohol use with an ethyl glucuronide (EtG) dipstick that is positive for 3 days after heavy drinking, and INH pill-taking using the IsoScreen urine test to test for 24-hour INH ingestion, thereby creating an opportunity to test incentive-based interventions during IPT among heavy drinkers. We propose leveraging two established cohorts of persons with HIV in Uganda for a randomized 2x2 factorial trial among HIV/TB co-infected adults with heavy alcohol use (n=800 persons. 400 each U01 cohort). Aim 1 is to determine whether economic incentives contingent on reduced alcohol use assessed by POC EtG tests conducted at INH refill visits reduces heavy alcohol use over six months of IPT compared to the control. Aim 2 is to determine whether economic incentives contingent on INH positive POC urine tests at these visits compared to the control increases IPT adherence over six months. Aim 3 is to examine the longer-term impact of the intervention on HIV virologic suppression, and examine mediators of an effect. Primary outcomes will be self-reported heavy alcohol use augmented by phosphatidylethanol (PEth) concentrations, and INH adherence, measured using medication event monitoring system (MEMS), with additional measurements of pill ingestion by INH levels in hair samples. Using incentive- based interventions to reduce alcohol use and increase medication safety in low-income settings is novel. This study to optimize IPT in HIV/TB co-infected drinkers will provide new information on low-cost strategies to reduce alcohol use and increase IPT adherence in low-income countries.

抽象的 结核病是全世界艾滋病毒感染者死亡的主要原因。在全球范围内，大约 25% 的人 艾滋病毒感染者是酗酒者，酗酒会使患结核病的风险增加 3 倍 与不饮酒相比，饮酒的艾滋病毒感染者患结核病的风险较高。六个月的 异烟肼 (INH) 预防性治疗 (IPT) 可将结核病发病率和死亡率降低 30-50%，较阳性药物高 30-50% 抗逆转录病毒治疗（ART）的影响。然而，INH 可能对肝脏有毒，因此许多重度酒精 东非等资源有限地区的用户无法获得 IPT。此外，酗酒者还 ART 依从性较差，数据表明 IPT 依从性也有所下降。因此需要采取干预措施 既可以减少饮酒，又可以增加 IPT 依从性，从而降低 INH 毒性、结核病发病率和 这一高危人群的死亡率。事实证明，利用激励措施促进健康行为是有效的 减少药物使用和提高艾滋病毒和结核病治疗方案依从性的高效方法 在高收入国家。减少饮酒可能会为安全有效地使用 IPT 创建一个窗口 降低肝毒性并提高 IPT 依从性；然而，对于 IPT 依从性的额外干预措施 可能需要。使用以减少饮酒或增加 INH 依从性为条件的激励措施 此前，由于缺乏对这些行为的可靠、快速的测试，资源有限的环境受到限制。 最近的技术进步允许使用乙酯对近期饮酒情况进行即时护理 (POC) 尿液检测 酗酒后 3 天葡萄糖醛酸 (EtG) 试纸呈阳性，并使用 INH 药片服用 IsoScreen 尿液​​检测可检测 24 小时 INH 摄入情况，从而创造一个测试基于激励的机会 对重度饮酒者进行 IPT 期间的干预。我们建议利用两个已建立的群体 乌干达艾滋病毒感染者在酗酒的同时感染艾滋病毒/结核病的成年人中进行了一项随机 2x2 析因试验 使用（n=800 人。每个 U01 队列 400 人）。目标 1 是确定经济激励是否取决于 通过 INH 补充就诊时进行的 POC EtG 测试评估的酒精使用减少量减少了重度酒精使用 与对照组相比，六个月的 IPT。目标 2 是确定经济激励是否取决于 与对照组相比，这些就诊时的 INH 阳性 POC 尿液检测可提高六个月内的 IPT 依从性。 目标 3 是检查干预措施对 HIV 病毒学抑制的长期影响，并检查 效应的中介者。主要结果将是自我报告的重度饮酒，并增加 使用药物事件监测测量磷脂酰乙醇 (PEth) 浓度和 INH 依从性 系统 (MEMS)，并通过头发样本中的 INH 水平对药丸摄入量进行额外测量。使用激励措施—— 在低收入环境中减少饮酒和提高用药安全性的干预措施是新颖的。这 优化 HIV/TB 合并感染饮酒者 IPT 的研究将提供关于低成本策略的新信息 减少饮酒并提高低收入国家的 IPT 依从性。