Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
Centre for Blood Research, University of British Columbia, Vancouver, Canada.
J Infect Dis. 2018 Feb 14;217(5):710-720. doi: 10.1093/infdis/jix618.
Maternal combination antiretroviral therapy (cART) during pregnancy could impact the health of human immunodeficiency virus (HIV)-exposed, HIV-uninfected (HEU) children, because some antiretrovirals cross the placenta and can inhibit telomerase. Our objective was to compare leukocyte telomere length (LTL) in HEU children and HIV-unexposed, HIV-uninfected (HUU) children at birth and in early life and to investigate any relationship with cART exposure.
HEU and HUU children's blood LTL was compared cross-sectionally at birth, and during the first three years of life. Longitudinal HEU LTL dynamics was evaluated over that same period.
At birth, the LTL in HEU children (n = 114) was not shorter than that in HUU children (n = 86), but female infants had longer LTL than male infants. Maternal cART (duration or type) showed no association with shorter infant LTL. Among 214 HEU children age- and sex-matched at a 1:1 ratio to HUU children, LTL declined similarly in both groups. In a longitudinal analysis, LTL attrition in HEU children was rapid from birth to 1 year of age and gradual thereafter. Zidovudine prophylaxis did not significantly alter LTL.
Our results indicate that from birth to 3 years of age, the LTL in HEU children is not negatively affected by exposure to maternal HIV infection and cART, at least not to the regimens used within this Canadian cohort, a reassuring finding.
母亲在怀孕期间接受联合抗逆转录病毒疗法(cART)可能会影响人类免疫缺陷病毒(HIV)暴露但未感染(HEU)儿童的健康,因为一些抗逆转录病毒药物可以穿过胎盘并抑制端粒酶。我们的目的是比较 HEU 儿童和未暴露于 HIV 的未感染(HUU)儿童出生时及生命早期的白细胞端粒长度(LTL),并研究其与 cART 暴露的关系。
我们在出生时以及生命的头三年对 HEU 和 HUU 儿童的血液 LTL 进行了横断面比较。在此期间,还评估了 HEU 儿童 LTL 的纵向动态变化。
在出生时,HEU 儿童(n=114)的 LTL 并不短于 HUU 儿童(n=86),但女性婴儿的 LTL 长于男性婴儿。母亲的 cART(持续时间或类型)与婴儿的 LTL 较短没有关联。在 214 名年龄和性别与 HUU 儿童 1:1 匹配的 HEU 儿童中,两组的 LTL 下降相似。在纵向分析中,HEU 儿童的 LTL 从出生到 1 岁时迅速下降,此后逐渐下降。齐多夫定预防治疗并未显著改变 LTL。
我们的研究结果表明,在出生到 3 岁期间,HEU 儿童的 LTL 不会因暴露于母体 HIV 感染和 cART 而受到负面影响,至少在加拿大队列中使用的方案中没有这种影响,这是一个令人安心的发现。