Lack of Atorvastatin Effect on Monocyte Gene Expression and Inflammatory Markers in HIV-1-infected ART-suppressed Individuals at Risk of non-AIDS Comorbidities.
Lack of Atorvastatin Effect on Monocyte Gene Expression and Inflammatory Markers in HIV-1-infected ART-suppressed Individuals at Risk of non-AIDS Comorbidities.
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DOI：
10.20411/pai.v6i2.461
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发表时间：
2021
影响因子：
--
通讯作者：
Collman RG
中科院分区：
文献类型：
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作者：
Yadav A;Kossenkov AV;Showe LC;Ratcliffe SJ;Choi GH;Montaner LJ;Tebas P;Shaw PA;Collman RG
尽管抗逆转录病毒治疗（ART）抑制了病毒，但许多艾滋病毒感染者仍有持续的单核细胞活化，这导致了包括神经认知和其他疾病在内的非艾滋病并发症。他汀类药物具有免疫调节特性，可能通过减少单核细胞活化而有益。我们之前对11名长期接受抗逆转录病毒治疗（HIV/ART）的HIV阳性患者进行了单核细胞基因表达和炎症标志物的研究，这些患者由于CD4+最低计数低（中位129个细胞/uL）和hsCRP升高而有非艾滋病并发症的风险。在这里，这些个体参加了一项双盲、随机、安慰剂对照的交叉研究，接受了12周的阿托伐他汀治疗。流式细胞术检测单核细胞表面标志物，ELISA和Luminex检测血浆介质，微阵列分析检测单核细胞基因表达。在主要结局指标中，12周的阿托伐他汀治疗导致CCR2+单核细胞意外增加（P=0.04），但不影响CD16+或CD163+单核细胞，也不影响血浆中CCL2/MCP-1或sCD14的水平。在次要结局中，阿托伐他汀治疗与血浆hsCRP （P=0.035）和IL-2R （P=0.012）降低相关。治疗还与CD14+单核细胞总数增加（P=0.015）、血浆CXCL9 （P=0.003）和IL-12 （P<0.001）增加相关。在基线时炎症标志物升高的亚组中也观察到类似的结果。阿托伐他汀治疗没有显著改变单核细胞基因表达或使异常基线转录模式正常化。在这项针对非艾滋病事件高危病毒血症HIV+个体的研究中，12周的阿托伐他汀治疗并没有使单核细胞基因表达模式正常化，也没有导致与非艾滋病合并症相关的单核细胞表面标记物或血浆介质的显著变化。
Many people living with HIV have persistent monocyte activation despite viral suppression by antiretroviral therapy (ART), which contributes to non-AIDS complications including neurocognitive and other disorders. Statins have immunomodulatory properties that might be beneficial by reducing monocyte activation. We previously characterized monocyte gene expression and inflammatory markers in 11 HIV-positive individuals on long-term ART (HIV/ART) at risk for non-AIDS complications because of low nadir CD4+ counts (median 129 cells/uL) and elevated hsCRP. Here, these individuals participated in a double-blind, randomized, placebo-controlled crossover study of 12 weeks of atorvastatin treatment. Monocyte surface markers were assessed by flow cytometry, plasma mediators by ELISA and Luminex, and monocyte gene expression by microarray analysis. Among primary outcome measures, 12 weeks of atorvastatin treatment led to an unexpected increase in CCR2+ monocytes (P=0.04), but did not affect CD16+ or CD163+ monocytes, nor levels in plasma of CCL2/MCP-1 or sCD14. Among secondary outcomes, atorvastatin treatment was associated with decreased plasma hsCRP (P=0.035) and IL-2R (P=0.012). Treatment was also associated with increased total CD14+ monocytes (P=0.015), and increased plasma CXCL9 (P=0.003) and IL-12 (P<0.001). Comparable results were seen in a subgroup that had inflammatory marker elevations at baseline. Atorvastatin treatment did not significantly alter monocyte gene expression or normalize aberrant baseline transcriptional patterns. In this study of aviremic HIV+ individuals at high risk of non-AIDS events, 12 weeks of atorvastatin did not normalize monocyte gene expression patterns nor lead to significant changes in monocyte surface markers or plasma mediators linked to non-AIDS comorbidities.