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首页> 外文期刊>AIDS Research and Human Retroviruses >CD4+ T-cell decline after the interruption of antiretroviral therapy in ACTG A5170 is predicted by differential expression of genes in the ras signaling pathway.
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CD4+ T-cell decline after the interruption of antiretroviral therapy in ACTG A5170 is predicted by differential expression of genes in the ras signaling pathway.

机译：ACTG A5170中断抗逆转录病毒治疗后CD4 + T细胞的下降可通过ras信号通路中基因的差异表达来预测。

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摘要

Patterns of expressed genes examined in cryopreserved peripheral blood mononuclear cells (PBMCs) of seropositive persons electing to stop antiretroviral therapy in the AIDS Clinical Trials Group Study A5170 were scrutinized to identify markers capable of predicting the likelihood of CD4+ T-cell depletion after cessation of antiretroviral therapy (ART). A5170 was a multicenter, 96-week, prospective study of HIV-infected patients with immunological preservation on ART who elected to interrupt therapy. Study entry required that the CD4 count was greater than 350 cells/mm(3) within 6 months of ART initiation. Median nadir CD4 count of enrollees was 436 cells/mm(3). Two cohorts, matched for clinical characteristics, were selected from A5170. Twenty-four patients with an absolute CD4 cell decline of less that 20% at week 24 (good outcome group) and 24 with a CD4 cell decline of >20% (poor outcome group) were studied. The good outcome group had a decline in CD4+ Tcell count that was 50% less than the poor outcome group. Significance analysis of microarrays identified differential gene expression (DE) in the two groups in data obtained from Affymetrix Human FOCUS GeneChips. DE was significantly higher in the poor outcome group than in the good outcome group. Prediction analysis of microarrays (PAM-R) identified genes that classified persons as to progression with greater than 80% accuracy at therapy interruption (TI) as well as at 24 weeks after TI. Gene set enrichment analysis (GSEA) identified a set of genes in the Ras signaling pathway, associated with the downregulation of apoptosis, as significantly upregulated in the good outcome group at cessation of ART. These observations identify specific host cell processes associated with differential outcome in this cohort after TI.
机译：在AIDS临床试验小组研究A5170中，对选择停止抗逆转录病毒治疗的血清阳性患者的冷冻保存的外周血单个核细胞（PBMC）中检查的表达基因的模式进行了仔细检查，以鉴定能够预测停止抗逆转录病毒后CD4 + T细胞耗尽的可能性的标记治疗（ART）。 A5170是一项多中心，为期96周的前瞻性研究，研究了选择中断治疗的接受HIV免疫保留的HIV感染患者。研究入选要求在ART起始6个月内CD4计数大于350细胞/ mm（3）。受试者的最低CD4计数中位数为436细胞/ mm（3）。从A5170中选择了两个针对临床特征匹配的队列。研究了24位在第24周时CD4细胞绝对下降少于20％的患者（好转组）和24位CD4细胞下降> 20％的患者（转归差的组）。结果良好的组的CD4 + T细胞计数下降比结果较差的组低50％。微阵列的意义分析确定了从Affymetrix Human FOCUS GeneChips获得的数据中两组中的差异基因表达（DE）。不良结局组的DE明显高于好结局组。对微阵列的预测分析（PAM-R）可以识别出在治疗中断（TI）以及TI后24周时，以超过80％的准确度对人进行分类的基因。基因集富集分析（GSEA）在Ras信号通路中确定了一组与凋亡下调相关的基因，在ART终止后的良好结果组中该基因显着上调。这些观察结果确定了在TI后该队列中与差异结果相关的特定宿主细胞过程。

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