子宫内抗逆转录病毒暴露的安全性：HIV 暴露但未感染的儿童的神经发育结局。
Safety of in-utero antiretroviral exposure: neurologic outcomes in children who are HIV-exposed but uninfected.
机构信息
Division of Infectious Diseases, Department of Pediatrics, University of Washington, Seattle Children's Hospital, Seattle, Washington.
Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
出版信息
AIDS. 2020 Jul 15;34(9):1377-1387. doi: 10.1097/QAD.0000000000002550.
OBJECTIVE
To evaluate whether there is an increased risk of neurologic diagnoses in children who are HIV-exposed but uninfected (CHEU) exposed in utero to specific antiretroviral medications.
DESIGN
Prospective cohort study of CHEU enrolled from 2007 to 2017.
METHODS
We evaluated children for neurologic case status, including microcephaly, febrile seizures, seizure disorders, ophthalmologic disorders, and other neurologic disorders. Adjusted relative risks (aRRs) were estimated for the association between in-utero antiretroviral exposure and neurologic case using log-binomial regression, accounting for potential confounders. Sensitivity analyses were conducted to evaluate robustness of findings.
RESULTS
Among 3747 eligible CHEU, 231 (6.2%) met neurologic case criteria (95% CI 5.4--7%). Most eligible children (86%) were exposed in utero to combination antiretroviral regimens. In adjusted models, children exposed to efavirenz at any time during pregnancy had higher risk of neurologic case status (aRR = 1.53, 95% CI 0.94--2.51). This association was stronger when comparing efavirenz exposure at conception to no exposure during pregnancy (aRR = 1.92, 95% CI 1.09--3.36) and considering follow-up and case diagnosis only through age 2 (aRR = 2.14, 95% CI 1.11--4.12). Children exposed to didanosine at conception and during the first trimester had increased risk of neurologic case status (aRR = 2.28, 95% CI 1.07--4.87 and aRR = 2.02, 95% CI 1.01--4.04, respectively), compared with didanosine-unexposed children. Children with dolutegravir exposure had some suggestion of increased risk of neurologic case (aRR = 2.43, 95% CI 0.75--7.84), which was observed consistently across several sensitivity analyses.
CONCLUSION
Efavirenz and didanosine exposure during pregnancy were associated with higher risk of neurologic abnormalities in CHEU, and dolutegravir exposure showed some suggestive associations, which warrant further monitoring.
目的
评估在子宫内暴露于特定抗逆转录病毒药物的 HIV 暴露但未感染（CHEU）的儿童是否存在神经诊断风险增加的情况。
设计
2007 年至 2017 年期间对 CHEU 进行前瞻性队列研究。
方法
我们评估了儿童的神经病例状态，包括小头畸形、热性惊厥、癫痫发作障碍、眼科疾病和其他神经疾病。使用对数二项式回归估计了在子宫内抗逆转录病毒暴露与神经病例之间的调整相对风险（aRR），并考虑了潜在的混杂因素。进行了敏感性分析以评估结果的稳健性。
结果
在 3747 名符合条件的 CHEU 中，有 231 名（6.2%）符合神经病例标准（95%CI 5.4-7%）。大多数合格的儿童（86%）在子宫内暴露于联合抗逆转录病毒方案。在调整后的模型中，在怀孕期间任何时候暴露于依非韦伦的儿童发生神经病例的风险更高（aRR=1.53，95%CI 0.94-2.51）。当将妊娠期间的依非韦伦暴露与怀孕期间无暴露进行比较时（aRR=1.92，95%CI 1.09-3.36），以及仅考虑到 2 岁时的随访和病例诊断（aRR=2.14，95%CI 1.11-4.12）时，这种关联更强。在妊娠和孕早期暴露于去羟肌苷的儿童发生神经病例的风险增加（aRR=2.28，95%CI 1.07-4.87 和 aRR=2.02，95%CI 1.01-4.04），与未暴露于去羟肌苷的儿童相比。暴露于多替拉韦的儿童的神经病例风险略有增加（aRR=2.43，95%CI 0.75-7.84），这在几次敏感性分析中都得到了一致的观察结果。
结论
妊娠期间依非韦伦和去羟肌苷暴露与 CHEU 中神经异常的风险增加相关，多替拉韦暴露显示出一些提示性关联，需要进一步监测。
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