Murray Daniel D, Suzuki Kazuo, Law Matthew, Trebicka Jonel, Neuhaus Jacquie, Wentworth Deborah, Johnson Margaret, Vjecha Michael J, Kelleher Anthony D, Emery Sean
The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia.
Department of Internal Medicine, University of Bonn, Bonn, Germany.
PLoS One. 2015 Oct 14;10(10):e0139981. doi: 10.1371/journal.pone.0139981. eCollection 2015.
The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals.
A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed.
None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR-145 correlated with nadir CD4+ T cell count.
No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection.
抗逆转录病毒疗法（ART）的使用显著降低了与HIV-1相关的发病率和死亡率。然而，与未感染HIV-1的人群相比，HIV-1感染者的发病率和死亡率有所上升，这似乎与统称为严重非艾滋病事件（SNAEs）的终末器官疾病有关。循环miRNA被报道为多种人类疾病状况（包括构成SNAEs的疾病）的有前景的生物标志物。我们的研究旨在调查所选miRNA在预测接受ART治疗的HIV-1感染者死亡率方面的潜力。
基于已发表的与构成SNAEs的人类疾病状况的关联选择了一组miRNA。这项病例对照研究比较了126例病例（治疗期间死亡的个体）和247例匹配对照（存活的个体）。病例和对照是两项关键HIV-1试验中接受ART治疗的参与者。通过RTqPCR测量血清中每种miRNA的相对丰度。通过逻辑回归分析评估与死亡率（全因、心血管和恶性肿瘤）的关联。还评估了miRNA与CD4 + T细胞计数、hs-CRP、IL-6和D-二聚体之间的相关性。
所选miRNA均与全因、心血管或恶性肿瘤死亡率无关。三种miRNA（miR -21、-122和-200a）的水平与IL-6相关，而miR-21也与D-二聚体相关。此外，miR -31、-150和-223的丰度与基线CD4 + T细胞计数相关，而相同的三种miRNA加上miR-145与最低点CD4 + T细胞计数相关。
在所研究的任何循环miRNA中均未发现与死亡率相关。这些结果使人怀疑循环miRNA作为HIV-1感染治疗参与者死亡率的早期预测指标或导致死亡的主要潜在疾病的有效性。
