Department of Infectious Diseases and Hepatology, Medical University of Lodz, Kniaziewicza 1/5, 91-347, Lodz, Poland.
Arch Immunol Ther Exp (Warsz). 2018 Aug;66(4):321-327. doi: 10.1007/s00005-018-0508-8. Epub 2018 Feb 21.
Damage of the mucosal barrier in HIV infection, microbial translocation, and immune activation can persist even in patients on successful antiretroviral therapy (ART) especially advanced late presenters. The aim of this study was to find factors that determine immune activation and bacterial translocation in HIV-infected advanced late presenters on suppressive ART. Forty-three late presenters (CD4 < 200 cells/µl prior to ART) on successful ART (more than 2 years of ART) with optimal and suboptimal CD4 recovery were enrolled into this study. The serum concentrations of intestinal fatty acid-binding peptide (I-FABP), zonulin-1, programmed cell death-1 protein (PCDP-1), and soluble (s)CD14 were measured using the ELISA test. We found higher serum levels of I-FABP and sCD14 in successfully antiretroviral-treated advanced late presenters compared to healthy subjects (p < 0.0001 and p = 0.0004). The serum concentration of PCDP-1 and zonulin-1 in HIV-infected patients did not differ from healthy controls. The levels of microbial translocation and immune activation markers were not associated with the degree of CD4 recovery. A serum concentration of I-FABP above 2.03 ng/ml was independently associated with a shorter ART (OR 0.78; p = 0.03). Older age was related to serum levels of sCD14 above 2.35 µg/ml (OR 1.1; p = 0.01). Higher serum levels of I-FABP and sCD14 in successfully antiretroviral-treated advanced late presenters compared to healthy subjects suggest an incomplete reconstruction of the intestinal barrier and sustained immune activation despite good CD4 recovery. It was not the CD4 level, but the length of the suppressive ART that was found to be associated with the restoration of the intestinal barrier.
在接受成功的抗逆转录病毒治疗（ART）的患者中，特别是晚期出现的患者，HIV 感染、黏膜屏障损伤、微生物易位和免疫激活仍可持续存在。本研究旨在寻找决定 HIV 感染晚期出现患者在抑制性 ART 下免疫激活和细菌易位的因素。本研究纳入了 43 名晚期出现患者（ART 前 CD4<200 个/µl），他们正在接受成功的 ART（超过 2 年的 ART），且 CD4 恢复情况为最佳或不理想。使用 ELISA 检测法测量血清中肠脂肪酸结合蛋白（I-FABP）、紧密连接蛋白-1（zonulin-1）、程序性死亡蛋白-1（PCDP-1）和可溶性 CD14（sCD14）的浓度。我们发现，与健康对照组相比，成功接受抗病毒治疗的晚期出现患者的血清 I-FABP 和 sCD14 水平更高（p<0.0001 和 p=0.0004）。HIV 感染患者的 PCDP-1 和 zonulin-1 血清浓度与健康对照组无差异。微生物易位和免疫激活标志物的水平与 CD4 恢复程度无关。血清 I-FABP 浓度高于 2.03ng/ml 与较短的 ART 独立相关（OR 0.78；p=0.03）。年龄较大与血清 sCD14 水平高于 2.35μg/ml 相关（OR 1.1；p=0.01）。与健康对照组相比，成功接受抗病毒治疗的晚期出现患者的血清 I-FABP 和 sCD14 水平较高，这表明尽管 CD4 恢复良好，但肠道屏障的重建仍不完全，免疫激活持续存在。与肠道屏障的恢复相关的是抑制性 ART 的持续时间，而不是 CD4 水平。
