DeBacker J Riley, Langenek Breanna, Bielefeld Eric C
VA RR&D National Center for Rehabilitative Auditory Research, VA Portland Healthcare System, Portland, OR, United States.
Oregon Hearing Research Center, Oregon Health and Science University, Portland, OR, United States.
Front Mol Neurosci. 2022 Jun 20;15:920528. doi: 10.3389/fnmol.2022.920528. eCollection 2022.
Over 27 million people worldwide currently receive daily antiretroviral therapy for the management of HIV/AIDS. In order to prevent the continued spread of HIV, the World Health Organization (WHO) recommends the use of highly active antiretroviral therapy by pregnant and nursing women. There is currently little research into the auditory effects of this therapy on children exposed during pregnancy and breastfeeding, and research to date on the direct effects of antiretroviral exposure on the auditory system is inconclusive. The current study examined the effects of WHO-recommended first-line antiretrovirals in a well-controlled animal model to evaluate the potential for auditory damage and dysfunction following these exposures. Female breeding mice were each exposed to one of four antiretroviral cocktails or a vehicle control once daily during pregnancy and breastfeeding. Offspring of these mice had their auditory status evaluated after weaning using auditory brainstem responses and distortion-product otoacoustic emissions (DPOAEs). Auditory brainstem response thresholds following antiretroviral exposure during gestation and breastfeeding showed elevated thresholds and increased wave latencies in offspring of exposed mice when compared to unexposed controls, but no corresponding decrease in DPOAE amplitude. These differences in threshold were small and so may explain the lack of identified hearing loss in antiretroviral-exposed children during hearing screenings at birth. Minimal degrees of hearing impairment in children have been correlated with decreased academic performance and impaired auditory processing, and so these findings, if also seen in human children, suggest significant implications for children exposed to antiretrovirals during development despite passing hearing screenings at birth.
目前，全球有超过2700万人每天接受抗逆转录病毒疗法来治疗艾滋病毒/艾滋病。为防止艾滋病毒持续传播，世界卫生组织（WHO）建议孕妇和哺乳期妇女使用高效抗逆转录病毒疗法。目前，关于这种疗法对孕期和哺乳期接触该疗法的儿童的听觉影响的研究很少，而且迄今为止，关于抗逆转录病毒药物暴露对听觉系统的直接影响的研究尚无定论。本研究在一个严格控制的动物模型中检验了WHO推荐的一线抗逆转录病毒药物的影响，以评估这些暴露后听觉损伤和功能障碍的可能性。雌性繁殖小鼠在怀孕和哺乳期间每天接受四种抗逆转录病毒鸡尾酒之一或载体对照。这些小鼠的后代在断奶后使用听觉脑干反应和畸变产物耳声发射（DPOAE）评估其听觉状态。与未暴露的对照组相比，孕期和哺乳期暴露于抗逆转录病毒药物的后代的听觉脑干反应阈值显示阈值升高，波潜伏期延长，但DPOAE振幅没有相应降低。这些阈值差异很小，这可能解释了在出生时听力筛查中未发现抗逆转录病毒药物暴露儿童听力损失的原因。儿童轻度听力障碍与学业成绩下降和听觉处理受损有关，因此，如果在人类儿童中也观察到这些结果，表明尽管在出生时通过了听力筛查，但发育过程中暴露于抗逆转录病毒药物的儿童仍有重大影响。
