Masiá Mar, Padilla Sergio, Fernández Marta, Barber Xavier, Moreno Santiago, Iribarren José Antonio, Portilla Joaquín, Peña Alejandro, Vidal Francesc, Gutiérrez Félix
*Infectious Diseases Unit, Hospital General de Elche, Universidad Miguel Hernández, Alicante, Spain; †Infectious Diseases Research Lab, Hospital General de Elche, Elche, Spain; ‡Statistics, Centro de Investigación Operativa, Universidad Miguel Hernández, Alicante, Spain; §Infectious Diseases Service, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain; ‖Infectious Diseases Unit, Hospital Universitario de Donostia, San Sebastián, Spain; ¶Infectious Diseases Unit, Hospital General Universitario de Alicante, Alicante, Spain; #Infectious Diseases Unit, Hospital Universitario San Cecilio, Camino de la Almazara 11, 03203 Elche, Granada, Spain; and **Infectious Diseases Unit, Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain.
J Acquir Immune Defic Syndr. 2017 Jun 1;75(2):e36-e44. doi: 10.1097/QAI.0000000000001287.
Recognition of potentially modifiable mechanisms implicated in the pathogenesis of non-AIDS events (NAEs) might help improve outcomes of HIV-infected individuals. HIV infection has been associated with increased oxidative stress. We assessed the association between F2-isoprostanes and serious NAEs, and whether they improve the predictive performance of inflammation and coagulation biomarkers.
Prospective multicenter cohort. Individuals who had an incident serious NAE and 2 sex- and age-matched participants with no events were selected. Measurement of F2-isoprostanes, highly sensitive C-reactive protein, interleukin-6, D-dimer, sCD14, sCD40, sCD163, and neopterin levels was performed in successive plasma samples collected from cohort inclusion.
Biomarkers were measured in 78 participants developing serious NAEs or death, and 151 subjects with no events. Adjusted levels of F2-isoprostanes, and also of highly sensitive C-reactive protein, sCD14, and D-dimer were higher in individuals who developed serious NAEs, including or not non-AIDS deaths. The same results were observed when only samples collected since the time of achieving virological suppression were analyzed. The additive incorporation of each biomarker, ending with F2-isoprostanes, in an adjusted model was associated with a graded and significant increase in the quality of model fitting, and 94% sensitivity, 33% specificity, and 0.77 accuracy to predict serious NAEs including non-AIDS-related death.
Oxidative stress is associated with a higher risk of serious NAEs, including non-AIDS deaths. This effect is independent and additive to biomarkers of inflammation, monocyte activation, and coagulation. Our results suggest that oxidative stress should be included among mechanisms to deal with to improve prognosis of HIV-infected individuals.
识别非艾滋病相关事件（NAEs）发病机制中可能可改变的机制，或许有助于改善HIV感染者的预后。HIV感染与氧化应激增加有关。我们评估了F2-异前列腺素与严重NAEs之间的关联，以及它们是否能提高炎症和凝血生物标志物的预测性能。
前瞻性多中心队列研究。选取发生严重NAE的个体以及2名性别和年龄匹配的无事件发生的参与者。对从队列纳入时开始连续采集的血浆样本进行F2-异前列腺素、高敏C反应蛋白、白细胞介素-6、D-二聚体、可溶性CD14、可溶性CD40、可溶性CD163和新蝶呤水平的检测。
对78名发生严重NAEs或死亡的参与者以及151名无事件发生的受试者进行了生物标志物检测。发生严重NAEs的个体，无论是否有非艾滋病相关死亡，其F2-异前列腺素以及高敏C反应蛋白、可溶性CD14和D-二聚体经调整后的水平均较高。仅分析自实现病毒学抑制后采集的样本时，也观察到了相同结果。在一个调整模型中，依次加入每个生物标志物（最后加入F2-异前列腺素）与模型拟合质量的分级显著提高相关，预测包括非艾滋病相关死亡的严重NAEs的敏感性为94%、特异性为33%、准确性为0.77。
氧化应激与严重NAEs（包括非艾滋病相关死亡）的较高风险相关。这种效应独立于炎症、单核细胞活化和凝血生物标志物，且具有累加性。我们的结果表明，氧化应激应被纳入改善HIV感染者预后需应对的机制之中。
