Kirmse Brian, Yao Tzy-Jyun, Hofherr Sean, Kacanek Deborah, Williams Paige L, Hobbs Charlotte V, Hazra Rohan, Borkowsky William, Van Dyke Russell B, Summar Marshall
1 Children's National Health System , Division of Genetics & Metabolism, Washington, DC.
2 Harvard T.H. Chan School of Public Health, Center for Biostatistics in AIDS Research , Boston, Massachusetts.
AIDS Res Hum Retroviruses. 2016 Apr;32(4):339-48. doi: 10.1089/AID.2015.0112. Epub 2016 Jan 19.
We sought to determine the prevalence of abnormal acylcarnitine profiles (ACP) in HIV-exposed uninfected (HEU) newborns and to explore the association of abnormal ACP with clinical laboratory outcomes and antiretroviral drug exposures. Clinically, ACP are used to assess for fatty acid oxidation (FAO) dysfunction and normal FAO is necessary for optimal fetal/neonatal growth and development. We analyzed serum ACP in 522 HEU neonates enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study of the Pediatric HIV/AIDS Cohort Study (PHACS) and evaluated the associations of abnormal ACP with in utero exposure to combination antiretroviral therapy (cART) in logistic regression models, adjusting for maternal demographic, disease, and behavioral characteristics. We evaluated the associations of abnormal ACP with laboratory parameters and measures of neurodevelopment and growth. Of 522 neonates, 89 (17%) had abnormal ACP. In adjusted analyses, in utero exposure to a protease inhibitor (PI) was associated with higher odds of having an abnormal ACP [adjusted odds ratio (aOR) = 2.35, 95% CI: 0.96, 5.76, p = 0.06] with marginal significance while exposure to a nonnucleoside reverse transcriptase inhibitor (NNRTI) was associated with lower odds (aOR = 0.23, 95% CI: 0.07, 0.80, p = 0.02). Mean ALT levels were slightly higher in those with abnormal ACP, but no differences in lactate, glucose, or CPK were observed. ACP status was not associated with neurodevelopment at 1 year or growth at 2 and 3 years of age. Abnormal ACP in HEU neonates are associated with exposure to PI-containing as opposed to NNRTI-containing antiretroviral (ARV) regimens but are not associated with serious postnatal clinical problems. Further studies are needed to determine the long-term health implications of abnormal acylcarnitine metabolism at birth in HEU children.
我们试图确定暴露于HIV但未感染（HEU）的新生儿中异常酰基肉碱谱（ACP）的患病率，并探讨异常ACP与临床实验室结果及抗逆转录病毒药物暴露之间的关联。临床上，ACP用于评估脂肪酸氧化（FAO）功能障碍，而正常的FAO对于胎儿/新生儿的最佳生长发育是必需的。我们分析了参与儿科HIV/AIDS队列研究（PHACS）的抗逆转录病毒治疗毒性监测（SMARTT）研究的522名HEU新生儿的血清ACP，并在逻辑回归模型中评估异常ACP与宫内暴露于联合抗逆转录病毒治疗（cART）之间的关联，同时对母亲的人口统计学、疾病和行为特征进行了调整。我们评估了异常ACP与实验室参数以及神经发育和生长指标之间的关联。在522名新生儿中，89名（17%）有异常ACP。在调整分析中，宫内暴露于蛋白酶抑制剂（PI）与异常ACP的较高几率相关[调整后的优势比（aOR）=2.35，95%置信区间：0.96，5.76，p=0.06]，具有边缘显著性，而暴露于非核苷类逆转录酶抑制剂（NNRTI）与较低几率相关（aOR=0.23，95%置信区间：0.07，0.80，p=0.02）。ACP异常者的平均ALT水平略高，但未观察到乳酸、葡萄糖或CPK的差异。ACP状态与1岁时的神经发育或2岁和3岁时的生长无关。HEU新生儿的异常ACP与含PI而非含NNRTI的抗逆转录病毒（ARV）方案暴露相关，但与严重的出生后临床问题无关。需要进一步研究以确定HEU儿童出生时异常酰基肉碱代谢对长期健康的影响。
