Alcohol & Zinc Impact on Inflammatory Markers in HIV Disease - Russia ARCH Cohort

描述（由申请人提供）：HIV感染者大量饮酒可能加速HIV疾病进展和终末器官疾病，其中一个主要的解释途径是通过增强微生物易位和炎症/凝血改变。大量饮酒和艾滋病毒感染都是微生物易位的原因，细菌产物渗漏穿过胃肠道膜的过程导致破坏性免疫激活。酒精可以通过缺锌直接导致微生物易位。影响30-50%酒精依赖者的低锌水平与免疫功能下降和艾滋病毒疾病进展有关。在hiv感染者中，高水平的微生物易位（通过可溶性CD14测量）和炎症/凝血改变（通过D-二聚体测量）均与死亡风险增加相关。重要的是，在艾滋病毒感染者中，在横断面研究中，大量饮酒也与较高水平的d -二聚体显著相关。值得注意的是，抗逆转录病毒治疗（ART）的开始与d -二聚体水平的降低有关。然而，以下内容尚不清楚：饮酒与这些独立于ART的生物标志物之间是否存在纵向关系；补充锌能提高生物标志物水平吗？回答这些问题需要在艾滋病毒感染普遍、酗酒和目前抗逆转录病毒治疗使用有限的环境中进行。由于俄罗斯的艾滋病毒流行时间相对较短，而且还在不断扩大，艾滋病毒治疗基础设施不断完善，人均酒精消费量巨大，圣彼得堡是开展这项研究的理想场所。因此，作为乌干达、俄罗斯、波士顿酒精网络艾滋病毒/艾滋病酒精研究合作（URBAN ARCH）联盟的一部分，我们试图从最近完成的niaaa资助的俄罗斯hiv感染重度饮酒者随机对照试验（RCT）的参与者中创建俄罗斯ARCH队列，并进行以下研究：[1]评估饮酒与微生物易位生物标志物（sCD14）和炎症/凝血改变（d -二聚体）之间的纵向关联；在一项队列（锌）研究中实施锌干预，这是一项双盲、安慰剂对照的随机对照试验，旨在确定短期补充锌是否会导致较低的生物标志物水平，以及其效果是否因饮酒而异。这些研究将阐明酒精与关键生物标志物之间的关系，并评估一种实用的治疗方法，即补充锌，作为hiv感染的重度饮酒者的治疗方法。

DESCRIPTION (provided by applicant): Heavy alcohol consumption in an HIV-infected person may accelerate HIV disease progression and end organ disease with one leading explanatory pathway being via enhanced microbial translocation and inflammation/altered coagulation. Heavy alcohol consumption and HIV infection are both causes of microbial translocation, the process by which bacterial products leak across the gastrointestinal membrane with resultant destructive immune activation. Alcohol can lead to microbial translocation directly through zinc deficiency. Low zinc levels, affecting 30-50% of alcohol dependent persons, are associated w ith reduced immune function and HIV disease progression. Among HIV-infected people, high levels of microbial translocation (as measured by soluble CD14) and inflammation/altered coagulation (as measured by D- dimer) are each associated with an increased risk of death. Of importance, among HIV-infected persons, heavy drinking is also significantly associated with higher levels of D-dimer in cross-sectional studies. Of note, initiation of antiretroviral therapy (ART) is associated with a reduction in D-dimer levels. Yet the following is not known: is there a longitudinal relationship between alcohol consumption and these biomarkers independent of ART; and does zinc supplementation improve biomarker levels? Answering these questions requires a setting with prevalent HIV infection, heavy alcohol use and limited current ART use. As Russia has a relatively young, expanding HIV epidemic, a growing HIV treatment infrastructure and enormous per capita alcohol consumption, St. Petersburg is a setting where this research is possibi e. Thus, as part of the Uganda, Russia, Boston Alcohol Network for Alcohol Research Collaboration on HIV/AIDS (URBAN ARCH) Consortium, we seek to create the Russia ARCH cohort from participants of a recently completed NIAAA-funded randomized controlled trial (RCT) of HIV-infected Russian heavy drinkers and perform the following: [1] an assessment of the longitudinal association between alcohol consumption and biomarkers of microbial translocation (sCD14) and inflammation/altered coagulation (D-dimer); [2] implementation of the Zinc Intervention Nested in a Cohort (ZINC) study, a double-blinded, placebo controlled, RCT to determine if short term zinc supplementation results in lower biomarker levels and whether the effects differ based on alcohol consum ption. These studies will clarify the association between alcohol and key biomarkers overtime and evaluate a pragmatic treatment, zinc supplementation, as a therapy in HIV-infected heavy drinkers.