HIV infection is characterized by CD4+ T-cells depletion related to gut damage, microbial translocation, immune activation and intestinal and systemic low-grade inflammation. With the use of antiretroviral treatment, these alterations in HIV+ patients reach similar levels to HIV- controls. However, almost 20% patients have deficient immune reconstitution of CD4+ T-cells, which make them more susceptible to develop non-AIDS and AIDS comorbidities. HIV+ patients on ART, with sustained virologic control were grouped according to their immune reconstitution as: immunological responders (n = 18) and immunological non-responders (n = 18); also, HIV- controls were enrolled (n = 14). CD4+ and CD8+ T-cell activation (HLA-DR+ and CD38+ single and co-expression) were measured by flow cytometry. Serum levels of sCD14, sCD163, lipopolysaccharide, I-FABP, sST2, as well as fecal levels of calprotectin, lactoferrin and secretory IgA were evaluated by ELISA. Levels of C-reactive protein were determined by a high sensibility singleplex bead-based immunoassay. Serum and fecal concentrations of proinflammatory cytokines were quantified by multiplex bead-based immunoassay. HLA-DR+ and CD38+ co-expression, as well as median fluorescence intensity in CD4+ and CD8+ T-cells subpopulations was greater in immunological non-responders group, after normalization and fold change calculation. Similarly, this group presented higher levels of sCD14, C-reactive protein, as well as fecal calprotectin and lactoferrin. Furthermore, both HIV+ groups showed elevated levels of proinflammatory cytokines in stool. Our data suggests that despite the virologic control, HIV+ patients under treatment with deficient immune reconstitution showed elevation of both innate and T-cells immune activation, as well as intestinal and systemic inflammation. However, some patients with CD4+ T-cells count above 350 cells/μL also presented these alterations. Future studies are necessary to evaluate the dynamics of multiple systemic and intestinal biomarkers in diverse types of HIV+ patients, as such as their clinical impact.

中文翻译：

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接受 ART 的 HIV+ 患者肠道和全身炎症生物标志物与免疫重建的关联

HIV 感染的特征是与肠道损伤、微生物易位、免疫激活以及肠道和全身性低度炎症相关的 CD4+ T 细胞耗竭。通过使用抗逆转录病毒治疗，HIV+ 患者的这些改变达到了与 HIV 对照相似的水平。然而，几乎 20% 的患者 CD4+ T 细胞的免疫重建不足，这使他们更容易患上非艾滋病和艾滋病合并症。接受 ART 且持续病毒学控制的 HIV+ 患者根据其免疫重建分为：免疫应答者（n = 18）和免疫无应答者（n = 18）；此外，还招募了 HIV 对照（n = 14）。通过流式细胞术测量 CD4+ 和 CD8+ T 细胞活化（HLA-DR+ 和 CD38+ 单表达和共表达）。sCD14、sCD163、脂多糖、I-FABP、sST2、以及通过ELISA评估粪便中钙卫蛋白、乳铁蛋白和分泌型IgA的水平。C 反应蛋白的水平通过高灵敏度单重珠免疫测定法确定。促炎细胞因子的血清和粪便浓度通过多重基于珠的免疫测定法进行量化。在归一化和倍数变化计算后，免疫无应答组的 HLA-DR+ 和 CD38+ 共表达以及 CD4+ 和 CD8+ T 细胞亚群中的中值荧光强度更大。同样，该组的 sCD14、C 反应蛋白以及粪便钙卫蛋白和乳铁蛋白水平更高。此外，两个 HIV+ 组均显示粪便中促炎细胞因子水平升高。我们的数据表明，尽管进行了病毒学控制，接受免疫重建缺陷治疗的 HIV+ 患者表现出先天和 T 细胞免疫激活以及肠道和全身炎症的升高。然而，一些 CD4+ T 细胞计数高于 350 个细胞/μL 的患者也出现了这些变化。未来的研究对于评估不同类型 HIV+ 患者中多种全身和肠道生物标志物的动态变化是必要的，例如它们的临床影响。