University Hospitals Cleveland Medical Center.
Rainbow Babies and Children's Hospital.
AIDS. 2020 Jun 1;34(7):1009-1018. doi: 10.1097/QAD.0000000000002505.
The pathophysiology of immune activation and its mechanisms in children living with perinatally acquired HIV (PHIV) in sub-Saharan Africa has been understudied.
We enrolled 101 children living with PHIV and 96 HIV-negative controls (HIV-). All participants were between 10 and 18 years of age with no known active infections. PHIVs were on ART with HIV-1 RNA level 400 copies/ml or less. We measured plasma and cellular markers of monocyte activation, T-cell activation (expression of CD38 and HLA-DR on CD4 and CD8), oxidized lipids, markers of gut integrity and fungal translocation. Spearman correlations and linear regression models were used.
Overall median (Q1; Q3) age was 13 years (11; 15) and 52% were girls. Groups were similar by age, sex and BMI. Median ART duration was 10 years (8; 11). PHIVs had higher monocyte and T-cell activation; higher sCD14 (P = 0.01) and elevated frequencies of nonclassical monocytes (P < 0.001 for both). Markers of systemic inflammation (hsCRP), fungal translocation (BDG), intestinal permeability (zonulin) and oxidized lipids (ox LDL) correlated with monocyte and T-cell activation in PHIV (≤0.05). After adjusting for age, sex, ART duration, protease inhibitor and nonnucleoside reverse transcriptase inhibitor use, a modest association between BDG and activated CD4 T cells was observed (β=0.65, P < 0.01). Oxidized LDL was inversely associated with activated T cells, inflammatory and nonclassical monocytes (P < 0.01).
Ugandan children with perinatally acquired HIV with viral suppression have evidence of ongoing immune activation. Intestinal barrier dysfunction and fungal translocation may be involved in chronic immune dysfunction.
在撒哈拉以南非洲地区，先天感染 HIV（PHIV）的儿童的免疫激活病理生理学及其机制尚未得到充分研究。
我们纳入了 101 名 PHIV 儿童和 96 名 HIV 阴性对照（HIV-）。所有参与者年龄均在 10 至 18 岁之间，且无已知活动性感染。PHIV 正在接受抗逆转录病毒治疗（ART），HIV-1 RNA 水平低于 400 拷贝/ml。我们测量了血浆和细胞单核细胞激活标志物、T 细胞激活标志物（CD4 和 CD8 上的 CD38 和 HLA-DR 表达）、氧化脂质、肠道完整性和真菌易位标志物。使用 Spearman 相关和线性回归模型。
总体中位数（Q1；Q3）年龄为 13 岁（11；15），52%为女孩。组间年龄、性别和 BMI 相似。ART 治疗中位时间为 10 年（8；11）。PHIV 具有更高的单核细胞和 T 细胞激活；更高的可溶性 CD14（P=0.01）和非经典单核细胞频率升高（均<0.001）。全身性炎症标志物（hsCRP）、真菌易位（BDG）、肠道通透性（zonulin）和氧化脂质（oxLDL）与 PHIV 的单核细胞和 T 细胞激活相关（≤0.05）。在校正年龄、性别、ART 治疗时间、蛋白酶抑制剂和非核苷类逆转录酶抑制剂使用后，BDG 与激活的 CD4 T 细胞之间存在适度关联（β=0.65，P<0.01）。氧化 LDL 与激活的 T 细胞、炎症性和非经典单核细胞呈负相关（P<0.01）。
在乌干达接受过母婴垂直传播的 HIV 病毒抑制的儿童中，存在持续的免疫激活证据。肠道屏障功能障碍和真菌易位可能与慢性免疫功能障碍有关。
