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HIV-RNA<50拷贝/毫升的接受抗逆转录病毒治疗的HIV阳性患者的先天免疫、可溶性标志物与代谢临床参数之间的关系

Relationship between innate immunity, soluble markers and metabolic-clinical parameters in HIV+ patients ART treated with HIV-RNA<50 cp/mL.

作者信息

Dentone Chiara, Fenoglio Daniela, Signori Alessio, Cenderello Giovanni, Parodi Alessia, Bozzano Federica, Guerra Michele, De Leo Pasqualina, Bartolacci Valentina, Mantia Eugenio, Orofino Giancarlo, Kalli Francesca, Marras Francesco, Fraccaro Paolo, Giacomini Mauro, Cassola Giovanni, Bruzzone Bianca, Ferrea Giuseppe, Viscoli Claudio, Filaci Gilberto, De Maria Andrea, Di Biagio Antonio

机构信息

Infectious Diseases, Sanremo Hospital, Sanremo, Italy; Center of Excellence for Biomedical Research, University of Genoa, Sanremo, Italy.

DIMI, Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.

出版信息

J Int AIDS Soc. 2014 Nov 2;17(4 Suppl 3):19718. doi: 10.7448/IAS.17.4.19718. eCollection 2014.

Abstract

INTRODUCTION

The persistence of immune activation and inflammation in HIV patients with HIV-RNA (VL) undetectable causes many co-morbidities [1-3]. The aim of this study is to correlate monocytes (m) and NK cell activation levels, soluble markers and oxidative stress with clinical, biochemical and metabolic data in HIV-1 infected patients with VL≤50 copies (cp)/mL on antiretroviral therapy.

MATERIALS AND METHODS

Multicentre, cross-sectional study in patients with VL≤50 cp/mL and on antiretroviral therapy by at least six months. We studied: activation/homing markers (CD38, HLA-DR, CCR-2, PDL-1) on inflammatory, intermediate, proinflammatory m; activatory receptors NKp30, NKp46 and HLA-DR on NK cells; soluble inflammatory (sCD14, adiponectina, MCP-1) and stress oxidative markers (dRoms, antiRoms). Univariate analyses are performed with non-parametric and Pearson tests. The significant correlations were adjusted for possible known confounding factors (smoking, Cytomegalovirus IgG serology, Raltegravir, Protease Inhibitor [PI] therapy and HCV-RNA) with multivariate analysis.

RESULTS

In the 68 patients the positive correlation between age and antiRoms was significant also after adjustment for PI use (p=0.05). The% CD8+T was associated with% proinflammatory m (p=0.043) and with their expression of CCR2 mean fluorescence intensity (MFI) (p=0.012). The% NKp46+ was positively correlated with CD4+T count (p=0.001). The fibrinogen was positively associated with dRoms (p=0.052) and the positive correlation between triglycerides and antiRoms has been confirmed (p<0.001); the impact of antiRoms on HDL/triglycerides ratio (p=0.006) was observed after adjustment for PI use. The BMI was associated with smoking (p=0.011). Only the maraviroc-treated patients showed minimal arterial pressure, fibrinogen and antiRoms lower (p=0.001, 0.004 e 0.006) and sCD14 values higher (p=0.029).

CONCLUSIONS

Patients with long history of HIV infection and stable immunological and virological status showed interactions between acquired and innate immunity activation; moreover, the levels of some metabolic and inflammatory parameters correlate with oxidative stress values and innate immunity activation. The age, BMI and smoking impact metabolic and immunological parameters. The correlations between antiretroviral drugs and clinical-immunological parameters need further confirmations.

摘要

引言

在HIV-RNA(病毒载量,VL)检测不到的HIV患者中,免疫激活和炎症持续存在会引发许多合并症[1-3]。本研究的目的是将HIV-1感染且病毒载量≤50拷贝(cp)/mL并接受抗逆转录病毒治疗的患者的单核细胞(m)和NK细胞激活水平、可溶性标志物及氧化应激与临床、生化和代谢数据相关联。

材料与方法

对病毒载量≤50 cp/mL且接受抗逆转录病毒治疗至少6个月的患者进行多中心横断面研究。我们研究了:炎症性、中间型、促炎性m上的激活/归巢标志物(CD38、HLA-DR、CCR-2、PDL-1);NK细胞上的激活受体NKp30、NKp46和HLA-DR;可溶性炎症标志物(sCD14、脂联素、MCP-1)和氧化应激标志物(dRoms、抗Roms)。采用非参数检验和Pearson检验进行单变量分析。通过多变量分析对可能的已知混杂因素(吸烟、巨细胞病毒IgG血清学、拉替拉韦、蛋白酶抑制剂[PI]治疗和HCV-RNA)进行校正后,得出显著相关性。

结果

在68例患者中,校正PI使用情况后,年龄与抗Roms之间的正相关性仍显著(p = 0.05)。CD8+T百分比与促炎性m百分比相关(p = 0.043),且与促炎性m的CCR2平均荧光强度(MFI)表达相关(p = 0.012)。NKp46+百分比与CD4+T细胞计数呈正相关(p = 0.001)。纤维蛋白原与dRoms呈正相关(p = 0.052),甘油三酯与抗Roms之间的正相关性得到证实(p < 0.001);校正PI使用情况后,观察到抗Roms对HDL/甘油三酯比值的影响(p = 0.006)。BMI与吸烟相关(p = 0.011)。仅接受马拉维罗治疗的患者显示出最低的动脉压、纤维蛋白原和抗Roms水平较低(p = 0.001、0.004和0.006),而sCD14值较高(p = 0.029)。

结论

有长期HIV感染病史且免疫和病毒学状态稳定的患者显示出获得性免疫和先天性免疫激活之间的相互作用;此外,一些代谢和炎症参数水平与氧化应激值及先天性免疫激活相关。年龄、BMI和吸烟会影响代谢和免疫参数。抗逆转录病毒药物与临床免疫参数之间的相关性需要进一步证实。

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