Epidemiology, University of Washington, Seattle, WA.
Department of Pediatrics & Child Health, University of Nairobi, Nairobi, Kenya.
J Acquir Immune Defic Syndr. 2019 May 1;81(1):102-109. doi: 10.1097/QAI.0000000000001979.
Monocyte activation may contribute to neuronal injury in aviremic HIV-infected adults; data are lacking in children. We examined the relation between monocyte activation markers and early and long-term neurodevelopmental outcomes in early-treated HIV-infected children.
Prospective study of infant and child neurodevelopmental outcomes nested within a randomized clinical trial (NCT00428116) and extended cohort study in Kenya.
HIV-infected infants (N = 67) initiated antiretroviral therapy (ART) at age <5 months. Plasma soluble (s) CD163 (sCD163), sCD14, and neopterin were measured before ART (entry) and 6 months later. Milestone attainment was ascertained monthly during 24 months, and neuropsychological tests were performed at 5.8-8.2 years after initiation of ART (N = 27). The relationship between neurodevelopment and sCD163, sCD14, and neopterin at entry and 6 months after ART was assessed using Cox proportional hazards models and linear regression.
Infants with high entry sCD163 had unexpected earlier attainment of supported sitting (5 vs 6 months; P = 0.006) and supported walking (10 vs 12 months; P = 0.02) with trends in adjusted analysis. Infants with high 6-month post-ART sCD163 attained speech later (17 vs 15 months; P = 0.006; adjusted hazard ratio, 0.47; P = 0.02), threw toys later (18 vs 17 months; P = 0.01; adjusted hazard ratio, 0.53; P = 0.04), and at median 6.8 years after ART, had worse neuropsychological test scores (adj. mean Z-score differences, cognition, -0.42; P = 0.07; short-term memory, -0.52; P = 0.08; nonverbal test performance, -0.39, P = 0.05).
Before ART, monocyte activation may reflect transient neuroprotective mechanisms in infants. After ART and viral suppression, monocyte activation may predict worse short- and long-term neurodevelopment outcomes.
单核细胞激活可能导致无病毒性 HIV 感染成人的神经元损伤；但在儿童中缺乏相关数据。我们研究了早期治疗的 HIV 感染儿童中单核细胞激活标志物与早期和长期神经发育结局之间的关系。
前瞻性研究婴儿和儿童神经发育结局，嵌套在随机临床试验（NCT00428116）和肯尼亚的扩展队列研究中。
HIV 感染的婴儿（N = 67）在<5 个月时开始接受抗逆转录病毒治疗（ART）。在开始 ART（入组）前和 6 个月后测量血浆可溶性（s）CD163（sCD163）、sCD14 和新蝶呤。在 24 个月期间每月确定达到里程碑的情况，在开始 ART 后 5.8-8.2 年进行神经心理学测试（N = 27）。使用 Cox 比例风险模型和线性回归评估 ART 入组时和 6 个月后 sCD163、sCD14 和新蝶呤与神经发育的关系。
高入组 sCD163 的婴儿意外更早地达到支持坐姿（5 个月对 6 个月；P = 0.006）和支持行走（10 个月对 12 个月；P = 0.02），在调整分析中呈趋势。高 6 个月 post-ART sCD163 的婴儿语言发育较晚（17 个月对 15 个月；P = 0.006；调整后的危险比，0.47；P = 0.02），扔玩具较晚（18 个月对 17 个月；P = 0.01；调整后的危险比，0.53；P = 0.04），并且在中位数为 6.8 年后 ART，神经心理学测试评分较差（调整后的平均 Z 分数差异，认知，-0.42；P = 0.07；短期记忆，-0.52；P = 0.08；非言语测试表现，-0.39，P = 0.05）。
ART 前，单核细胞激活可能反映了婴儿的短暂神经保护机制。ART 后和病毒抑制后，单核细胞激活可能预测短期和长期神经发育结局较差。
