Lewis Joanna, Payne Helen, Walker A Sarah, Otwombe Kennedy, Gibb Diana M, Babiker Abdel G, Panchia Ravindre, Cotton Mark F, Violari Avy, Klein Nigel, Callard Robin E
CoMPLEX, University College London, London, United Kingdom.
NIHR Health Protection Research Unit in Modelling Methodology, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
Front Immunol. 2017 Sep 20;8:1162. doi: 10.3389/fimmu.2017.01162. eCollection 2017.
Early treatment of HIV-infected children and adults is important for optimal immune reconstitution. Infants' immune systems are more plastic and dynamic than older children's or adults', and deserve particular attention. This study aimed to understand the response of the HIV-infected infant immune system to early antiretroviral therapy (ART) and planned ART interruption and restart.
Data from HIV-infected children enrolled the CHER trial, starting ART aged between 6 and 12 weeks, were used to explore the effect of ART on immune reconstitution. We used linear and non-linear regression and mixed-effects models to describe children's CD4 trajectories and to identify predictors of CD4 count during early and interrupted ART.
Early treatment arrested the decline in CD4 count but did not fully restore it to the levels observed in HIV-uninfected children. Treatment interruption at 40 or 96 weeks resulted in a rapid decline in CD4 T-cells, which on retreatment returned to levels observed before interruption. Naïve CD4 T-cell count was an important determinant of overall CD4 levels. A strong correlation was observed between thymic output and the stable CD4 count both before and after treatment interruption.
Early identification and treatment of HIV-infected infants is important to stabilize CD4 counts at the highest levels possible. Once stabilized, children's CD4 counts appear resilient, with good potential for recovery following treatment interruption. The naïve T-cell pool and thymic production of naive cells are key determinants of children's CD4 levels.
对感染HIV的儿童和成人进行早期治疗对于实现最佳免疫重建至关重要。婴儿的免疫系统比大龄儿童或成人的更具可塑性和动态性，值得特别关注。本研究旨在了解感染HIV的婴儿免疫系统对早期抗逆转录病毒治疗（ART）以及计划性ART中断和重新启动的反应。
来自参加CHER试验的感染HIV儿童的数据被用于探索ART对免疫重建的影响，这些儿童在6至12周龄时开始接受ART。我们使用线性和非线性回归以及混合效应模型来描述儿童的CD4轨迹，并确定早期和中断ART期间CD4计数的预测因素。
早期治疗阻止了CD4计数的下降，但未能将其完全恢复到未感染HIV儿童中观察到的水平。在40周或96周时中断治疗导致CD4 T细胞迅速下降，重新治疗后恢复到中断前观察到的水平。初始CD4 T细胞计数是总体CD4水平的重要决定因素。在治疗中断前后，胸腺输出与稳定的CD4计数之间均观察到强相关性。
对感染HIV的婴儿进行早期识别和治疗对于将CD4计数稳定在尽可能高的水平很重要。一旦稳定下来，儿童的CD4计数似乎具有恢复力，在治疗中断后有良好的恢复潜力。初始T细胞库和初始细胞的胸腺生成是儿童CD4水平的关键决定因素。
