Zinc for HIV Disease among Alcohol Users -An RCT in the Russia ARCH Cohort

描述（由申请人提供）：大量饮酒和HIV感染的组合与死亡率增加、HIV疾病进展、急性心肌梗死（AMI）和以炎症生物标志物水平增加为特征的促炎状态相关。大量饮酒和HIV感染都是微生物易位的原因，这是细菌产物从胃肠道（GI）穿过GI膜泄漏到门静脉循环的过程。微生物移位引起免疫激活，导致终末器官损伤。酒精可通过缺锌引起微生物易位。锌缺乏在HIV+重度饮酒者中很常见，并与高死亡率有关。锌补充剂是负担得起的，可用的，不干扰ART，并且药物不良反应最小。在动物模型中，锌减少了乙醇相关的微生物易位。在人类研究中，锌减缓了艾滋病的进展，降低了与死亡率密切相关的炎症生物标志物的水平。鉴于锌的潜在疗效，我们建议进行锌治疗HIV感染和慢性疾病（ZINC HIV），这是一项双盲随机对照试验，旨在评估250名HIV+俄罗斯人中补锌与安慰剂的疗效，这些人在入组时未经ART治疗，最近有酗酒史。我们将从乌干达俄罗斯波士顿酒精研究网络艾滋病毒/艾滋病酒精研究合作（URBAN AIDS-Consortium）研究中的俄罗斯队列中招募大部分参与者。我们的具体目标是测试与安慰剂相比，锌补充剂的功效：（1）通过VACS指数测量改善死亡率标志物;（2）通过CD 4细胞计数测量减缓HIV疾病进展;（3）通过Reynolds风险评分测量改善AMI风险标志物;（4）通过血清生物标志物测量降低微生物易位和炎症水平。我们假设，与安慰剂相比，接受锌补充的患者将具有显著较低的AMI和死亡风险（通过VACS指数和Reynolds风险评分测量）;较高的CD 4细胞计数;较低水平的微生物易位和炎症的生物标志物。重要的是，如果我们的假设是真的，补锌最终可能成为一种标准的预防性治疗，补充艾滋病毒+人群中的酒精干预措施，即使在资源有限的环境中。

DESCRIPTION (provided by applicant): The combination of heavy alcohol consumption and HIV infection is associated with increased mortality, HIV disease progression, acute myocardial infarction (AMI) and a proinflammatory state characterized by increased biomarker levels of inflammation. Heavy alcohol use and HIV infection are both causes of microbial translocation, the process by which bacterial products from the gastrointestinal (GI) tract leak across the GI membrane to the portal circulation. Microbial translocation causes immune activation leading to end organ damage. Alcohol can cause microbial translocation via zinc deficiency. Zinc deficiency is common among HIV+ heavy drinkers and linked to high mortality rates. Zinc supplementation is affordable, available, does not interfere with ART, and has minimal adverse drug reactions. In animal models zinc reduces ethanol associated microbial translocation. In human studies zinc slows HIV disease progression and reduces levels of inflammatory biomarkers which are strongly linked to mortality. Given zinc's potential efficacy we propose to conduct Zinc for INflammation and Chronic disease in HIV (ZINC HIV), a double-blinded randomized controlled trial to assess the efficacy of zinc supplementation vs. placebo among 250 HIV+ Russians, who are ART-naive at enrollment and have a recent history of heavy drinking. We will recruit most of our participants from the Russia cohort within the Uganda Russia Boston Alcohol Network for Alcohol Research Collaboration on HIV/AIDS (URBAN ARCH) Consortium study. Our specific aims will test the efficacy of zinc supplementation, compared to placebo to (1) improve markers of mortality as measured by the VACS index; (2) slow HIV disease progression as measured by CD4 cell count; (3) improve markers of AMI risk as measured by the Reynolds risk score; and (4) lower levels of microbial translocation and inflammation as measured by serum biomarkers. We hypothesize that as compared with placebo, patients receiving zinc supplementation will have significantly lower AMI and mortality risk as measured by the VACS index and Reynolds risk scores; higher CD4 cell counts; lower levels of biomarkers for microbial translocation and inflammation. Importantly, if our hypotheses are true, zinc supplementation could ultimately become a standard adjunctive therapy complementing alcohol interventions among HIV+ persons even in resource limited environments.