HIV 感染、HCV 合并感染和饮酒：与微生物易位和免疫激活的关联。
HIV Infection, HCV Coinfection, and Alcohol Use: Associations with Microbial Translocation and Immune Activation.
机构信息
Center for Alcohol and Addiction Studies , Brown University, Providence, Rhode Island.
Center for Cognitive Aging and Memory , University of Florida, Gainesville, Florida.
出版信息
Alcohol Clin Exp Res. 2019 Jun;43(6):1126-1134. doi: 10.1111/acer.14032. Epub 2019 Apr 29.
BACKGROUND
Human immunodeficiency virus (HIV) infection and heavy drinking independently promote microbial translocation and inflammation. However, it is not known how alcohol use may affect these processes in people living with HIV (PLWH). This study tested the hypothesis that alcohol exacerbates innate immune dysfunction in PLWH.
METHODS
Participants were 75 PLWH and 34 uninfected controls. Groups were recruited to have similar proportions of nondrinkers, moderate drinkers, and heavy drinkers. Substance use data and plasma samples were collected at up to 3 visits over a 5-year study period. Recent alcohol use was assessed with the Timeline Followback Interview. Biomarkers of microbial translocation (lipopolysaccharide, LPS) and immune activation (lipopolysaccharide binding protein, LBP; soluble CD14, sCD14; soluble CD163, sCD163) were quantified using enzyme-linked immunosorbent assays. Analyses tested 2 hypotheses: (i) that biomarker levels would be significantly higher in PLWH than controls with comparable alcohol use and (ii) that current alcohol use would exacerbate biomarker elevations in PLWH. The second analysis included the interaction of alcohol use with hepatitis C virus (HCV) coinfection.
RESULTS
Groups were matched on alcohol use, smoking, and other drug use. All biomarkers were significantly higher in PLWH relative to controls (LBP: p = 0.005; LPS: p = 0.014; sCD14: p < 0.001; sCD163: p < 0.001). In PLWH, alcohol use showed a significant, positive association with sCD163, but not with other biomarkers. However, the interaction of alcohol use with HCV coinfection was significant for all biomarkers (LBP: p = 0.002; LPS: p = 0.026; sCD14: p = 0.0004; sCD163: p = 0.001). In pairwise tests with sequential Bonferroni correction, HIV/HCV coinfected individuals who drank heavily had significantly higher sCD163 compared to coinfected nondrinkers and to HIV monoinfected nondrinkers, moderate drinkers, and heavy drinkers (ps < 0.005). Coinfected moderate drinkers had significantly higher sCD163 than each monoinfected group (ps < 0.003). In addition, sCD14 was significantly higher in coinfected moderate drinkers than coinfected nondrinkers (p = 0.027).
CONCLUSIONS
As predicted, PLWH had higher levels of LBP, LPS, sCD14, and sCD163 than uninfected individuals with similar alcohol use. In PLWH, alcohol by itself was significantly associated only with higher sCD163. However, heavy or moderate alcohol use was associated with elevations in macrophage activation (sCD163) and monocyte activation (sCD14) in HIV/HCV coinfected individuals.
背景
人类免疫缺陷病毒（HIV）感染和大量饮酒都会促进微生物易位和炎症。然而，目前尚不清楚酒精使用如何影响 HIV 感染者（PLWH）的这些过程。本研究检验了酒精是否会加重 PLWH 固有免疫功能障碍的假设。
方法
研究对象为 75 名 PLWH 和 34 名未感染对照者。根据有无饮酒、饮酒量和饮酒频率，将研究对象分为非饮酒者、适度饮酒者和重度饮酒者。在 5 年的研究期间，通过 3 次随访采集研究对象的物质使用数据和血浆样本。最近的饮酒情况使用时间线回溯访谈进行评估。采用酶联免疫吸附试验（ELISA）检测微生物易位标志物（脂多糖，LPS）和免疫激活标志物（脂多糖结合蛋白，LBP；可溶性 CD14，sCD14；可溶性 CD163，sCD163）。分析测试了两个假设：（i）具有相似酒精使用量的 PLWH 与对照组相比，标志物水平会显著更高；（ii）当前的酒精使用会加重 PLWH 中标志物的升高。第二项分析包括酒精使用与丙型肝炎病毒（HCV）合并感染的相互作用。
结果
在酒精使用、吸烟和其他药物使用方面，各组匹配良好。PLWH 的所有标志物水平均显著高于对照组（LBP：p=0.005；LPS：p=0.014；sCD14：p<0.001；sCD163：p<0.001）。在 PLWH 中，酒精使用与 sCD163 呈显著正相关，但与其他标志物无关。然而，酒精使用与 HCV 合并感染的相互作用对所有标志物均有显著影响（LBP：p=0.002；LPS：p=0.026；sCD14：p=0.0004；sCD163：p=0.001）。通过顺序 Bonferroni 校正的两两比较，与 HCV 合并感染的重度饮酒者与合并感染的非饮酒者和 HIV 单感染的非饮酒者、适度饮酒者和重度饮酒者相比，sCD163 水平显著更高（p<0.005）。合并感染的适度饮酒者与每个单感染组相比，sCD163 水平显著更高（p<0.003）。此外，与合并感染的非饮酒者相比，合并感染的中度饮酒者 sCD14 水平显著升高（p=0.027）。
结论
正如预测的那样，与具有相似酒精使用量的未感染者相比，PLWH 的 LBP、LPS、sCD14 和 sCD163 水平更高。在 PLWH 中，酒精本身仅与 sCD163 升高显著相关。然而，重度或中度饮酒与 HIV/HCV 合并感染个体的巨噬细胞活化（sCD163）和单核细胞活化（sCD14）升高有关。
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