婴儿期异烟肼预防治疗不会对 HIV 暴露但未感染儿童的生长发育产生不良影响：来自随机对照试验的二次分析数据。

Isoniazid preventive therapy during infancy does not adversely affect growth among HIV-exposed uninfected children: Secondary analysis of data from a randomized controlled trial.

机构信息

Department of Population and Community Health, School of Public Health, University of North Texas Health Science Center, Fort Worth, Texas, United States of America.

Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington, United States of America.

出版信息

PLoS One. 2024 Aug 16;19(8):e0293708. doi: 10.1371/journal.pone.0293708. eCollection 2024.

DOI:10.1371/journal.pone.0293708

PMID:39150949

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11329125/

Abstract

BACKGROUND

Isoniazid preventive therapy (IPT) decreases risk of tuberculosis (TB) disease; impact on long-term infant growth is unknown. In a recent randomized trial (RCT), we assessed IPT effects on infant growth without known TB exposure.

METHODS

The infant TB Infection Prevention Study (iTIPS) trial was a non-blinded RCT among HIV-exposed uninfected (HEU) infants in Kenya. Inclusion criteria included age 6-10 weeks, birthweight ≥2.5 kg, and gestation ≥37 weeks. Infants in the IPT arm received 10 mg/kg isoniazid daily for 12 months, while the control trial received no intervention; post-trial observational follow-up continued through 24 months of age. We used intent-to-treat linear mixed-effects models to compare growth rates (weight-for-age z-score [WAZ] and height-for-age z-score [HAZ]) between trial arms.

RESULTS

Among 298 infants, 150 were randomized to IPT, 47.6% were females, median birthweight was 3.4 kg (interquartile range [IQR] 3.0-3.7), and 98.3% were breastfed. During the 12-month intervention period and 12-month post-RCT follow-up, WAZ and HAZ declined significantly in all children, with more HAZ decline in male infants. There were no growth differences between trial arms, including in sex-stratified analyses. In longitudinal linear analysis, mean WAZ (β = 0.04 [95% CI:-0.14, 0.22]), HAZ (β = 0.14 [95% CI:-0.06, 0.34]), and WHZ [β = -0.07 [95% CI:-0.26, 0.11]) z-scores were similar between arms as were WAZ and HAZ growth trajectories. Infants randomized to IPT had higher monthly WHZ increase (β to 24 months 0.02 [95% CI:0.01, 0.04]) than the no-IPT arm.

CONCLUSION

IPT administered to HEU infants did not significantly impact growth outcomes in the first two years of life.

摘要

背景

异烟肼预防治疗（IPT）可降低结核病（TB）发病风险；但对长期婴儿生长的影响尚不清楚。在最近的一项随机试验（RCT）中，我们评估了IPT 对无已知 TB 暴露的婴儿生长的影响。

方法

婴儿结核病感染预防研究（iTIPS）试验是肯尼亚一项针对 HIV 暴露但未感染（HEU）婴儿的非盲 RCT。纳入标准包括年龄 6-10 周、出生体重≥2.5kg 和胎龄≥37 周。IPT 组的婴儿每天接受 10mg/kg 异烟肼治疗 12 个月，而对照组则不接受干预；试验后观察性随访持续到 24 个月龄。我们使用意向治疗线性混合效应模型比较了试验组之间的生长速度（体重-年龄 z 评分[WAZ]和身高-年龄 z 评分[HAZ]）。

结果

在 298 名婴儿中，150 名被随机分配到 IPT 组，47.6%为女性，中位出生体重为 3.4kg（四分位距[IQR]3.0-3.7），98.3%为母乳喂养。在 12 个月的干预期和 RCT 后 12 个月的随访期间，所有儿童的 WAZ 和 HAZ 均显著下降，男婴 HAZ 下降更为明显。两组之间没有生长差异，包括在性别分层分析中。在纵向线性分析中，WAZ（β=0.04[95%CI:-0.14,0.22]）、HAZ（β=0.14[95%CI:-0.06,0.34]）和 WHZ[β=-0.07[95%CI:-0.26,0.11]）z 评分相似，WAZ 和 HAZ 生长轨迹也相似。与无 IPT 组相比，被随机分配到 IPT 组的婴儿在 24 个月时的 WHZ 月增长更高（β=0.02[95%CI:0.01,0.04]）。