Relevance of Interleukin-6 and D-Dimer for Serious Non-AIDS Morbidity and Death among HIV-Positive Adults on Suppressive Antiretroviral Therapy.
Relevance of Interleukin-6 and D-Dimer for Serious Non-AIDS Morbidity and Death among HIV-Positive Adults on Suppressive Antiretroviral Therapy.
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DOI：
10.1371/journal.pone.0155100
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
INSIGHT SMART/ESPRIT/SILCAAT Study Group
中科院分区：
文献类型：
--
作者：
Grund B;Baker JV;Deeks SG;Wolfson J;Wentworth D;Cozzi-Lepri A;Cohen CJ;Phillips A;Lundgren JD;Neaton JD;INSIGHT SMART/ESPRIT/SILCAAT Study Group
尽管有有效的抗逆转录病毒治疗（ART），艾滋病毒阳性个体患严重非艾滋病疾病（心血管、肝脏和肾脏疾病以及癌症）的风险增加，这可能部分是由于持续的炎症和/或凝血。为了估计通过减少炎症和/或凝血的治疗可能实现的严重非艾滋病疾病或任何原因死亡的潜在风险降低，我们检查了白细胞介素-6（IL-6）、D-二聚体和高敏C的相关性反应蛋白（hsCRP）水平与3个大型队列中的严重非艾滋病疾病或死亡。采用考克斯回归分析研究了接受抑制性ART治疗的HIV阳性成人中IL-6、D-二聚体和hsCRP水平与严重非AIDS疾病或死亡的关系。校正年龄、性别、研究和回归稀释偏倚（由于人内生物标志物变异性）的风险比（HR）用于预测与较低的IL-6和D-二聚体“通常”水平相关的严重非AIDS疾病或死亡的风险降低。在平均4.9年的随访中，3766名参与者中有260人经历了严重的非艾滋病疾病或死亡。IL-6、D-二聚体和hsCRP分别与严重非AIDS疾病或死亡风险相关，HR分别为1.45（95% CI：1.30 - 1.63）、1.28（95% CI：1.14 - 1.44）和1.17（95% CI：1.09 - 1.26）/2倍高生物标志物水平。在联合模型中，IL-6和D-二聚体与严重非AIDS疾病或死亡独立相关，3个队列和严重非AIDS事件类型的结果一致。IL-6和D-二聚体与严重的非艾滋病疾病或死亡的相关性被分级，并在整个随访期间持续存在。如果IL-6和D-二聚体水平降低25%，联合生物标志物模型估计严重非艾滋病疾病或死亡的风险降低37%（95%CI：28 - 46%），如果这种关系是因果关系。IL-6和D-二聚体都与严重的非艾滋病疾病或HIV阳性的病毒抑制成人死亡独立相关。这表明，降低IL-6和D-二聚体水平的治疗可能会大大降低抑制性ART患者的发病率和死亡率。需要临床试验来验证这一假设。
Despite effective antiretroviral treatment (ART), HIV-positive individuals are at increased risk of serious non-AIDS conditions (cardiovascular, liver and renal disease, and cancers), perhaps due in part to ongoing inflammation and/or coagulation. To estimate the potential risk reduction in serious non-AIDS conditions or death from any cause that might be achieved with treatments that reduce inflammation and/or coagulation, we examined associations of interleukin-6 (IL-6), D-dimer, and high-sensitivity C-reactive protein (hsCRP) levels with serious non-AIDS conditions or death in 3 large cohorts. In HIV-positive adults on suppressive ART, associations of IL-6, D-dimer, and hsCRP levels at study entry with serious non-AIDS conditions or death were studied using Cox regression. Hazard ratios (HR) adjusted for age, gender, study, and regression dilution bias (due to within-person biomarker variability) were used to predict risk reductions in serious non-AIDS conditions or death associated with lower “usual” levels of IL-6 and D-dimer. Over 4.9 years of mean follow-up, 260 of the 3766 participants experienced serious non-AIDS conditions or death. IL-6, D-dimer and hsCRP were each individually associated with risk of serious non-AIDS conditions or death, HR = 1.45 (95% CI: 1.30 to 1.63), 1.28 (95% CI: 1.14 to 1.44), and 1.17 (95% CI: 1.09 to 1.26) per 2x higher biomarker levels, respectively. In joint models, IL-6 and D-dimer were independently associated with serious non-AIDS conditions or death, with consistent results across the 3 cohorts and across serious non-AIDS event types. The association of IL-6 and D-dimer with serious non-AIDS conditions or death was graded and persisted throughout follow-up. For 25% lower “usual” IL-6 and D-dimer levels, the joint biomarker model estimates a 37% reduction (95% CI: 28 to 46%) in the risk of serious non-AIDS conditions or death if the relationship is causal. Both IL-6 and D-dimer are independently associated with serious non-AIDS conditions or death among HIV-positive adults with suppressed virus. This suggests that treatments that reduce IL-6 and D-dimer levels might substantially decrease morbidity and mortality in patients on suppressive ART. Clinical trials are needed to test this hypothesis.