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携带者的主要死因。在全球范围内，大约25%的人 携带艾滋病毒的人是酗酒者，大量饮酒与患结核病的风险增加3倍相关 因此，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)预防疗法(IPT)使结核病发病率和死亡率比阳性降低30-50% 抗逆转录病毒治疗(ART)的影响。然而，异烟肼对肝脏有毒性，因此对许多重酒都有毒性。 东非等资源有限地区的用户不能享受互联网技术。此外，酗酒者还 更差的抗逆转录病毒治疗依从性和数据表明，IPT依从性也有所下降。因此，需要进行干预以 两者都减少了酒精使用并增加了IPT的依从性，从而降低了异烟肼毒性、结核病发病率和 这一高危人群的死亡率。使用激励措施来促进健康的行为已被证明是 一种减少药物使用和改善对艾滋病毒和结核病方案的依从性的高效方法 在高收入国家。减少酒精使用可能通过以下方式为安全和有效地使用IPT创造一个窗口 降低肝脏毒性和增加IPT依从性；然而，对IPT依从性的额外干预 可能是需要的。使用激励措施的条件是减少饮酒或增加对异烟肼的依从性 资源有限的设置以前一直受到这些行为缺乏可靠、快速测试的限制。 最近的技术进步允许对最近酒精使用的护理点(POC)尿液进行乙基 大量饮酒后3天呈阳性的葡萄糖醛酸(EtG)试纸，以及服用异烟肼药丸时使用 IsoScreen尿液测试以测试24小时异烟肼摄入量，从而创造了测试基于激励的机会 对酗酒者进行IPT期间的干预。我们建议利用两个既定的群体 在乌干达对HIV/TB合并感染且酗酒的成年人进行随机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 通过在INH再灌装就诊时进行的POC EtG测试评估减少酒精使用量 与对照组相比，IPT治疗6个月。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INH阳性的POC尿检增加了6个月内IPT的依从性。 目标3是检查干预对艾滋病毒病毒学抑制的长期影响，并检查 一种效果的调解人。主要结果将是自我报告的重度酒精使用量增加 使用药物事件监测测量磷脂酰乙醇(PEH)浓度和异烟肼依从性 (MEMS)，通过头发样本中异烟肼水平的额外测量来测量药丸摄入量。使用激励措施- 在低收入环境中减少酒精使用和提高用药安全性的干预措施是新的。这 优化HIV/TB混合感染饮酒者的IPT的研究将提供有关低成本策略的新信息 在低收入国家减少酒精使用并增加对IPT的遵守。

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.