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

摘要 结核病是全世界艾滋病毒感染者死亡的主要原因。全球约25%的人 艾滋病毒感染者是酗酒者，酗酒与结核病风险高出3倍有关。 与不饮酒相比，饮酒的艾滋病毒感染者患结核病的风险很高。六个月 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%， 抗逆转录病毒疗法（ART）的影响。然而，INH可能对肝脏有毒，因此许多重型酒精 在诸如东非的资源有限的环境中的用户不被提供IPT。此外，酗酒者 ART依从性较差，数据表明IPT依从性也降低。因此，需要采取干预措施， 既减少了酒精的使用，又增加了IPT的依从性，从而减少了INH的毒性、结核病的发病率和 这一高危人群的死亡率。使用激励措施来促进健康行为已被证明是 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。减少酒精使用可以为安全有效地使用IPT创造一个窗口， 降低肝毒性和增加IPT依从性;然而，IPT依从性的额外干预 可能需要。使用以减少酒精使用或增加INH依从性为条件的激励措施， 资源有限的环境以前受到缺乏对这些行为的可靠、快速测试的限制。 最新的技术进步允许使用乙基纤维素对最近使用酒精的护理点（POC）尿液检测 葡萄糖醛酸苷（EtG）试纸在大量饮酒后3天呈阳性，并使用 IsoScreen尿液检测，用于检测24小时INH摄入量，从而为基于激励的测试创造机会 在重度饮酒者中进行IPT干预。我们建议利用两个已建立的人群 在乌干达的艾滋病毒感染者中进行了一项随机2x2析因试验，该试验在患有重度酒精的艾滋病毒/结核病合并感染成人中进行 使用（n=800人）。每个U 01队列400例）。目标1是确定经济激励是否取决于 通过在INH补充访视时进行的POC EtG测试评估的酒精使用减少， 六个月的IPT与对照组相比。目标2是确定经济激励是否取决于 与对照组相比，这些访视时INH阳性POC尿液检测增加了6个月内的IPT依从性。 目的3是检查干预措施对艾滋病毒抑制的长期影响，并检查 一种效果的媒介。主要结果将是自我报告的重度酒精使用增加， 磷脂酰乙醇（PEth）浓度和INH依从性，使用药物事件监测测量 系统（MEMS），通过头发样本中的INH水平对药丸摄入进行额外测量。使用激励- 在低收入环境中减少饮酒和提高药物安全性的基础性干预措施是新颖的。这 优化HIV/TB合并感染饮酒者IPT的研究将提供有关低成本策略的新信息， 在低收入国家减少饮酒并提高IPT依从性。

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.