MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London.
Department of International Public Health, Liverpool School of Tropical Medicine, Liverpool, UK.
AIDS. 2018 Sep 10;32(14):1977-1982. doi: 10.1097/QAD.0000000000001905.
To investigate CD4 cell count recovery following ART initiation in perinatally HIV-infected children diagnosed in later childhood.
Observational prospective cohort study of newly diagnosed children aged 6-15 in Harare, Zimbabwe.
Participants were enrolled into a cohort at seven primary healthcare clinics between January 2013 and January 2015. ART was initiated according to national guidelines and CD4 cell counts were performed 6-monthly over 18 months. The relationship between CD4 cell count and time on ART was investigated using regression analysis with fixed (population) and random (individual) effects, and age at ART initiation as a covariate.
Of the 307 participants who initiated ART, the median age at initiation was 11.7 years (interquartile range 9.6-13.8). The addition of an individual intercept and slope as random effects significantly improved the model fit compared with a fixed effects-only model. CD4 response (using a square-root transformation) was best modelled using a two-knot linear spline, with significant effects of time on ART and age at ART initiation. Younger children had a higher CD4 cell count at ART initiation (-17.9 cells/μl per year of age), an accelerated increase during the first 3 months on ART (-38.9 cells/μl per year of age at day 84), and a sustained higher CD4 cell count.
Earlier ART initiation in older children is associated with accelerated CD4 cell count recovery and lasting immune reconstitution. Our findings support WHO guidance recommending ART initiation in all children, irrespective of disease stage and CD4 cell count.
研究在儿童后期诊断为围生期感染艾滋病毒的儿童中，开始抗逆转录病毒治疗（ART）后 CD4 细胞计数的恢复情况。
在津巴布韦哈拉雷的 7 个初级保健诊所对新诊断为 6-15 岁的儿童进行了观察性前瞻性队列研究。
参与者于 2013 年 1 月至 2015 年 1 月期间被纳入该队列。根据国家指南启动 ART，在 18 个月内每 6 个月进行一次 CD4 细胞计数。使用固定（人群）和随机（个体）效应的回归分析以及 ART 起始时的年龄作为协变量，研究 CD4 细胞计数与 ART 时间之间的关系。
在 307 名开始接受 ART 的参与者中，起始年龄的中位数为 11.7 岁（四分位距 9.6-13.8）。添加个体截距和斜率作为随机效应可显著改善模型拟合，而不是仅使用固定效应的模型。使用平方根转换，CD4 反应（CD4 response）最好使用双结线性样条进行建模，ART 时间和 ART 起始时的年龄具有显著影响。年龄较小的儿童在开始接受 ART 时 CD4 细胞计数较高（每年年龄减少 17.9 个细胞/μl），在前 3 个月接受 ART 时的增加更快（第 84 天的年龄每年增加 38.9 个细胞/μl），并且持续的 CD4 细胞计数较高。
在年龄较大的儿童中更早开始 ART 与 CD4 细胞计数的加速恢复和持续的免疫重建有关。我们的研究结果支持世卫组织的指导意见，即无论疾病阶段和 CD4 细胞计数如何，均应在所有儿童中启动 ART。
