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中国艾滋病毒/艾滋病感染者头发中的类固醇、内源性大麻素水平及其比值生物标志物可预测病毒抑制情况。

Hair levels of steroid, endocannabinoid, and the ratio biomarkers predict viral suppression among people living with HIV/AIDS in China.

作者信息

Chu Liuxi, Liu Shuaifeng, Wu Yan, Yang Jin, Qiao Shan, Zhou Yuejiao, Deng Huihua, Li Xiaoming, Shen Zhiyong

机构信息

Department of Brain and Learning Science, School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China; Key Laboratory of Child Development and Learning Science (Southeast University), Ministry of Education, Nanjing 210096, China; Institute of Child Development and Education, Research Center for Learning Science, Southeast University, Nanjing 210096, China.

Guangxi Center for Disease Control and Prevention, Nanning 530028, China.

出版信息

Clin Chim Acta. 2022 Oct 1;535:143-152. doi: 10.1016/j.cca.2022.08.023. Epub 2022 Aug 27.

Abstract

BACKGROUND

Predicting viral suppression early is crucial to improving treatment outcomes among people living with HIV/AIDS (PLWH) in clinics. Viral suppression is affected by stress, making stress indicators a potential predictive factor. Most of previous studies used the self-report questionnaire as stress indicators, but there were great drawbacks due to its subjective. In contrast, end products of neuroendocrine systems such as hypothalamic-pituitaryadrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes and endogenous cannabinoid system (ECS) that involved in regulating stress as objective stress indicators are urgently needed to predict viral suppression. Therefore, this study aimed to investigate whether neuroendocrine indictors can strongly predict viral suppression among PLWH in China.

METHODS

This cross-sectional study recruited 1198 PLWH on antiretroviral therapy (ART) in Guangxi, China. The concentrations of steroids (i.e., cortisol, cortisone, dehydroepiandrosterone, testosterone and progesterone) and endocannabinoids (i.e., N-arachidonoyl-ethanolamine and 1-arachidonyl glycerol) in hair were quantitated using the LC-APCI-MS/MS method. To screen biomarkers that were used to predict viral suppression, association between hair biomarkers and viral suppression was examined by Mann-Whitney U test and partial correlation analyses. Receiver operating characteristic (ROC) curves and binary logistic regression based on the optimal classification threshold determined with ROC curves were used to estimate the prediction effects of the screened biomarkers on viral suppression (HIV-1 RNA < 200 copies/mL).

RESULTS

Hair levels of dehydroepiandrosterone (DHEA), and N-arachidonoyl-ethanolamine (AEA), and the cortisol to DHEA ratio exhibited significant intergroup differences (ps < 0.05) and were correlated with HIV viral load (ps < 0.05). Hair DHEA concentrations strongly predicted viral suppression, showing good classification performance (area under the ROC curve = 0.651, p < 0.01) and strong predictive utility (adjusted odd ratio = 2.324, 95 % confidence interval = 1.211-4.899, p < 0.05) with an optimal threshold of 10.5 pg/mg. A hair AEA concentration of 2.4 pg/mg was the optimal threshold for predicting viral suppression based on good classification performance (area under the ROC curve = 0.598, p < 0.05) and predictive power (adjusted odd ratio = 2.124, 95 % confidence interval = 1.045-4.244, p < 0.05). In hair levels of cortisol to DHEA, viral suppression was observed to be highly predictive, with a threshold of 10.5 pg/mg being optimal for classification (area under the ROC curve = 0.624, p < 0.05) and prediction (adjusted odd ratio = 0.421, 95 % confidence interval = 0.201-0.785, p < 0.05).

CONCLUSION

Hair levels of DHEA, and AEA and the cortisol to DHEA ratio were screened and verified to have significant predictive power with optimal thresholds for predicting viral suppression in a large-scale cohort. The data may provide new insights into predictors of successful virological outcomes and inform public health intervention and clinical practice to assist PLWH in achieving and sustaining viral suppression.

摘要

背景

早期预测病毒抑制对于改善临床中人类免疫缺陷病毒/艾滋病(PLWH)感染者的治疗效果至关重要。病毒抑制受压力影响,使压力指标成为潜在的预测因素。以往大多数研究使用自我报告问卷作为压力指标,但因其主观性存在很大缺陷。相比之下,迫切需要涉及调节压力的神经内分泌系统的终产物,如下丘脑 - 垂体 - 肾上腺(HPA)轴、下丘脑 - 垂体 - 性腺(HPG)轴和内源性大麻素系统(ECS)作为客观压力指标来预测病毒抑制。因此,本研究旨在调查神经内分泌指标是否能有力地预测中国PLWH中的病毒抑制情况。

方法

这项横断面研究在中国广西招募了1198名接受抗逆转录病毒治疗(ART)的PLWH。使用LC - APCI - MS/MS方法对头发中的类固醇(即皮质醇、可的松、脱氢表雄酮、睾酮和孕酮)和内源性大麻素(即N - 花生四烯酰乙醇胺和1 - 花生四烯酰甘油)浓度进行定量。为筛选用于预测病毒抑制的生物标志物,通过曼 - 惠特尼U检验和偏相关分析检查头发生物标志物与病毒抑制之间的关联。基于用ROC曲线确定的最佳分类阈值的受试者工作特征(ROC)曲线和二元逻辑回归用于估计筛选出的生物标志物对病毒抑制(HIV - 1 RNA < 200拷贝/mL)的预测效果。

结果

头发中的脱氢表雄酮(DHEA)、N - 花生四烯酰乙醇胺(AEA)水平以及皮质醇与DHEA的比值表现出显著的组间差异(p < 0.05),并且与HIV病毒载量相关(p < 0.05)。头发DHEA浓度有力地预测了病毒抑制,显示出良好的分类性能(ROC曲线下面积 = 0.651,p < 0.01)和强大的预测效用(调整后的比值比 = 2.324,95%置信区间 = 1.211 - 4.899,p < 0.05),最佳阈值为10.5 pg/mg。基于良好的分类性能(ROC曲线下面积 = 0.598,p < 0.05)和预测能力(调整后的比值比 = 2.124,95%置信区间 = 1.045 - 4.244,p < 0.05),头发AEA浓度为2.4 pg/mg是预测病毒抑制的最佳阈值。在头发皮质醇与DHEA水平方面,观察到病毒抑制具有高度预测性,阈值为10.5 pg/mg时分类效果最佳(ROC曲线下面积 = 0.624,p < 0.05)且预测效果良好(调整后的比值比 = 0.421,95%置信区间 = 0.201 - 答案0.785,p < 0.05)。

结论

头发中的DHEA、AEA水平以及皮质醇与DHEA的比值经过筛选和验证,在大规模队列中具有显著的预测能力,且具有预测病毒抑制的最佳阈值。这些数据可能为成功的病毒学结果的预测因素提供新的见解,并为公共卫生干预和临床实践提供参考,以帮助PLWH实现并维持病毒抑制。

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