BACKGROUND The multifactorial mechanisms driving negative health outcomes among risky drinkers with HIV may include immunosenescence. Immunosenescence, aging of the immune system, may be accentuated in HIV and leads to poor outcomes. The liver regulates innate immunity and adaptive immune tolerance. HIV-infected people have high prevalence of liver-related comorbidities. We hypothesize that advanced liver fibrosis/cirrhosis is associated with alterations in T-cell subsets consistent with immunosenescence. METHODS ART-naïve people with HIV with a recent history of heavy drinking were recruited into a clinical trial of zinc supplementation. Flow cytometry was used to characterize T-cell subsets. The two primary dependent variables were CD8+ and CD4+ T-cells expressing CD28-CD57+ (senescent cell phenotype). Secondary dependent variables were CD8+ and CD4+ T-cells expressing CD45RO + CD45RA- (memory phenotype), CD45RO-CD45RA+ (naïve phenotype), and the naïve phenotype to memory phenotype T-cell ratio (lower ratios associated with immunosenescence). Advanced liver fibrosis/cirrhosis was defined as FIB-4 > 3.25, APRI≥1.5, or Fibroscan measurement ≥10.5 kPa. Analyses were conducted using multiple linear regression adjusted for potential confounders. RESULTS Mean age was 34 years; 25% female; 88% hepatitis C. Those with advanced liver fibrosis/cirrhosis (N = 25) had higher HIV-1 RNA and more hepatitis C. Advanced liver fibrosis/cirrhosis was not significantly associated with primary or secondary outcomes in adjusted analyses. CONCLUSIONS Advanced liver fibrosis/cirrhosis was not significantly associated with these senescent T-cell phenotypes in this exploratory study of recent drinkers with HIV. Future studies should assess whether liver fibrosis among those with HIV viral suppression and more advanced, longstanding liver disease is associated with changes in these and other potentially senescent T-cell subsets.

中文翻译：

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大量饮酒的 HIV 感染俄罗斯人的肝纤维化和加速免疫功能障碍（免疫衰老） - 一项观察性横断面研究。

背景 在感染 HIV 的高危饮酒者中导致负面健康结果的多因素机制可能包括免疫衰老。免疫衰老，即免疫系统的老化，可能在 HIV 中加重并导致不良结果。肝脏调节先天免疫和适应性免疫耐受。HIV感染者的肝脏相关合并症发病率很高。我们假设晚期肝纤维化/肝硬化与符合免疫衰老的 T 细胞亚群改变有关。方法 招募近期有大量饮酒史的未接受过治疗的 HIV 感染者参加锌补充剂的临床试验。流式细胞术用于表征 T 细胞亚群。两个主要因变量是表达 CD28-CD57+（衰老细胞表型）的 CD8+ 和 CD4+ T 细胞。次要因变量是表达 CD45RO + CD45RA-（记忆表型）、CD45RO-CD45RA+（幼稚表型）的 CD8+ 和 CD4+ T 细胞，以及幼稚表型与记忆表型 T 细胞的比率（与免疫衰老相关的较低比率）。晚期肝纤维化/肝硬化定义为 FIB-4 > 3.25，APRI≥1.5，或 Fibroscan 测量值≥10.5 kPa。使用针对潜在混杂因素进行调整的多元线性回归进行分析。结果平均年龄为 34 岁；25% 女性；88% 的丙型肝炎。晚期肝纤维化/肝硬化患者（N = 25）具有更高的 HIV-1 RNA 和更多的丙型肝炎。在调整后的分析中，晚期肝纤维化/肝硬化与主要或次要结果没有显着相关性。结论 在这项对近期感染 HIV 的饮酒者的探索性研究中，晚期肝纤维化/肝硬化与这些衰老的 T 细胞表型没有显着相关性。未来的研究应评估 HIV 病毒抑制和更晚期、长期肝病患者的肝纤维化是否与这些和其他潜在衰老 T 细胞亚群的变化有关。