Sorbonne Universités, UPMC Univ Paris-6, Inserm UMR_S938, ICAN, APHP Hôpital Tenon and Saint-Antoine, 27 rue Chaligny, F-75571 Paris cedex 12, France.
IAME, UMR 1137, Université Paris Diderot, Sorbonne Paris Cité, Unité de Coordination du Risque Épidémique et Biologique, Assistance Publique-Hôpitaux de Paris, 16 rue Henri Huchard, F-75890 Paris cedex 18, France.
J Antimicrob Chemother. 2015;70(6):1816-24. doi: 10.1093/jac/dkv036. Epub 2015 Mar 1.
The objective of this study was to analyse the respective roles of personal factors and HIV infection markers on the systemic immune activation/inflammatory profile of long-term antiretroviral treatment-controlled patients.
A panel of soluble immune activation/inflammatory biomarkers was measured in 352 HIV-infected treatment-controlled patients from the APROCO-COPILOTE cohort, all of whom were started on a PI in 1997-99 and had a final evaluation 11 years later, and in 59 healthy controls.
A total of 81.5% of the patients were male, with the following characteristics: median age 49 years; 620 CD4 cells/mm(3); 756 CD8 cells/mm(3); CD4/CD8 ratio 0.81; BMI 23.0 kg/m(2); waist-to-hip ratio 0.95. Markers of inflammation-high-sensitivity (hs) IL-6 (median and IQR) (1.3 pg/L, 0.7-2.6), hs C-reactive protein (CRP) (2.1 mg/L, 0.9-4.5) and D-dimer (252 ng/mL, 177-374)-were elevated compared with healthy controls (P < 0.001) and strongly related to each other, as were markers of immune activation [soluble (s) CD14 (1356 ng/mL, 1027-1818), β2-microglobulin (2.4 mg/L, 2.0-3.1) and cystatin-C (0.93 mg/L, 0.82-1.1)]. Inflammatory and immune activation markers were also associated with each other. In HIV-infected patients: age was related to D-dimer, β2-microglobulin and cystatin-C levels; being a smoker was related to increased IL-6 and cystatin-C; and BMI and waist-to-hip ratio were related to CRP. Conversely, markers of HIV infection, current CD4 or CD8 values, CD4 nadir, CD4/CD8 ratio, AIDS stage at initiation of PIs, current viral load and duration of ART were not associated with immune activation/inflammation markers.
In these long-term treatment-controlled HIV-infected patients, all systemic markers of inflammation and immune activation were increased compared with healthy controls. This was related to demographic and behavioural factors, but not to markers of severity of the HIV infection. Intervention to decrease low-grade inflammation must thus prioritize modifiable personal factors.
本研究旨在分析个人因素和 HIV 感染标志物对长期接受抗逆转录病毒治疗且病毒得到控制的患者全身免疫激活/炎症特征的各自作用。
对来自 APROCO-COPILOTE 队列的 352 例接受抗逆转录病毒治疗且病毒得到控制的 HIV 感染患者进行了一系列可溶性免疫激活/炎症生物标志物的检测，所有患者均于 1997-1999 年开始接受蛋白酶抑制剂治疗，11 年后进行了最终评估，同时还对 59 例健康对照者进行了检测。
患者中共有 81.5%为男性，其特征如下：中位年龄 49 岁；CD4 细胞计数 620/mm3；CD8 细胞计数 756/mm3；CD4/CD8 比值 0.81；BMI 23.0 kg/m2；腰臀比 0.95。与健康对照组相比，炎症标志物高敏（hs）IL-6（中位数和 IQR）（1.3 pg/L，0.7-2.6）、hs-C 反应蛋白（CRP）（2.1 mg/L，0.9-4.5）和 D-二聚体（252 ng/mL，177-374）显著升高（P<0.001），且彼此之间高度相关，免疫激活标志物 [可溶性（s）CD14（1356 ng/mL，1027-1818）、β2-微球蛋白（2.4 mg/L，2.0-3.1）和胱抑素 C（0.93 mg/L，0.82-1.1）] 也存在同样的情况。炎症和免疫激活标志物也相互关联。在 HIV 感染患者中，年龄与 D-二聚体、β2-微球蛋白和胱抑素 C 水平相关；吸烟与 IL-6 和胱抑素 C 升高相关；BMI 和腰臀比与 CRP 相关。相反，HIV 感染标志物、当前 CD4 或 CD8 值、CD4 最低点、CD4/CD8 比值、开始使用蛋白酶抑制剂时的 AIDS 分期、当前病毒载量和 ART 持续时间与免疫激活/炎症标志物均无相关性。
在这些长期接受治疗且病毒得到控制的 HIV 感染患者中，所有全身炎症和免疫激活标志物均较健康对照者升高。这与人口统计学和行为因素相关，而与 HIV 感染严重程度标志物无关。因此，降低低度炎症的干预措施必须优先考虑可改变的个人因素。
