Alcohol's impact on immunological and virological profiles in HIV patients

摘要 酗酒和艾滋病毒感染都是世界范围内的主要健康问题。 酗酒在艾滋病毒感染者中比普通人群更普遍， 与抗逆转录病毒治疗(ART)依从性差和治疗不力密切相关 应答，导致艾滋病毒进展和抗逆转录病毒药物耐药性。更极端的是，酒精 过度消费和艾滋病毒感染独立损害胃肠道(GI) 粘膜屏障，导致肠道渗漏，允许微生物移位(MT)和 血液中微生物成分的积累，如脂多糖(LPS)。在艾滋病中 患者，MT是慢性免疫激活和炎症的原因，这是 进行性艾滋病毒感染，比血浆病毒载量更能预测疾病的结局。我们 假设过度饮酒和HIV感染会加剧MT，免疫 激活、炎症和病毒复制，从而加速艾滋病毒的疾病进展 感染和酒精性肝病，如酒精性肝炎(AH)。我们还假设 戒酒减缓或逆转艾滋病毒感染者的免疫和病毒学影响 酗酒者。我们已经组成了一个由六名科学家组成的研究团队， 在艾滋病和艾滋病的基础、翻译和临床研究方面的互补专业知识 免疫致病机制将在酒精领域进行改变范式的研究 艾滋病毒患者中的滥用(目标1，UH2阶段)。我们将招收感染艾滋病毒的酗酒者和 研究酒精对艾滋病毒相关合并症的影响的对照研究(目标2，UH2阶段)。 在UH2阶段招募的参与者将在UH3每6个月进行一次跟踪调查 相位纵向分析(目标3)。UH3阶段还将招募和跟进新的 参与者对酒精对MT、免疫细胞激活、 HIV感染的酗酒者的炎症、病毒复制和整合 AH(UH3相)。我们的建议具有很高的创新性，将极大地有助于小说的发展 HIV感染的酗酒者的生物标志物和治疗。生物样本库，在其 放在公共领域，将成为促进国家和地区发展的重要资源 酒精与艾滋病毒相互作用的国际调查。

Abstract Alcohol overconsumption and HIV infection are both major health issues worldwide. Alcohol abuse is more prevalent among HIV-infected people than the general population and strongly associated with poor adherence to antiretroviral therapy (ART) and poor treatment response, leading to HIV progression and ART drug resistance. More drastically, alcohol overconsumption and HIV infection independently damage the gastrointestinal (GI) tract mucosal barrier, leading to a leaky gut that allows microbial translocation (MT) and accumulation of microbial components such as lipopolysaccharide (LPS) in the blood. In HIV patients, MT is a cause of chronic immune activation and inflammation, which is a hallmark of progressive HIV infection and better predicts disease outcome than plasma viral load. We hypothesize that alcohol overconsumption and HIV infection exacerbate MT, immune activation, inflammation, and viral replication, thereby accelerating disease progression of HIV infection and alcoholic liver disease such as alcoholic hepatitis (AH). We also hypothesize that alcohol abstinence slows or reverses immunological and virological impacts in HIV-infected heavy drinkers. We have formed a research team consisting of six scientists with complementary expertise in basic, translational, and clinical research of AH and HIV immunopathogenesis to undertake paradigm-changing investigations in the field of alcohol abuse in HIV patients (Aim 1, UH2 phase). We will enroll HIV-infected heavy drinkers and controls for studying alcohol's impact on HIV-associated comorbidities (Aim 2, UH2 phase). Participants recruited in the UH2 phase will be followed up every 6-month for a year for UH3 phase longitudinal analysis (Aim 3). The UH3 phase will also recruit and follow up new participants to perform a longitudinal analysis of alcohol's impact on MT, immune cell activation, inflammation, and viral replication and integration in HIV-infected heavy drinkers with or without AH (UH3 Phase). Our proposal is highly innovative and will greatly aid in developing novel biomarkers and therapies of HIV-infected heavy drinkers. The biosample repository, upon its placement in the public domain, will become a significant resource for facilitating national and international investigations of alcohol and HIV interactions.