Adrenal Enzyme Impairment in Neonates and Adolescents Treated with Ritonavir and Protease Inhibitors for HIV Exposure or Infection
Adrenal Enzyme Impairment in Neonates and Adolescents Treated with Ritonavir and Protease Inhibitors for HIV Exposure or Infection
复制标题
DOI：
10.1159/000356916
复制
发表时间：
2014-01-01
影响因子：
3.2
通讯作者：
Polak, M.
中科院分区：
文献类型：
--
作者：
Kariyawasam, D.;Simon, A.;Polak, M.
背景：人类缺陷病毒（HIV）蛋白酶抑制剂（PIs）是一种广泛使用的药物，其药理作用可通过利托那韦（一种有效的细胞色素P450抑制剂）增强。我们之前报道过，hiv暴露的新生儿出生后预防性利托那韦- pi治疗与血浆17-羟基孕酮（17-OHP）和脱氢表雄酮硫酸（DHEA-S）升高有关。目的：进一步研究利托那韦- pi对新生儿和青少年肾上腺功能的影响。方法：前瞻性评价3例短期预防性治疗的hiv暴露新生儿和3例长期治疗的hiv感染青少年的肾上腺功能。分别测定ACTH给药前后血浆皮质醇、17-OHP、17- oh -孕烯醇酮、DHEA-S、雄烯二酮。结果：所有患者均无肾上腺功能障碍的临床症状。唯一在子宫内暴露于利托那韦- pi的新生儿血浆17-OHP升高高达3倍。6例患者中有4例17- oh -孕烯醇酮升高高达3.1倍，6例患者均出现DHEA- s升高（高达20.4倍）和/或DHEA升高（高达4.7倍）和/或雄烯二酮升高（高达5.2倍）。所有这些参数在治疗完成后都有所改善。结论：给予利托那韦- pi的新生儿和青少年表现出类似的肾上腺功能障碍特征，与多种肾上腺酶的影响一致。考虑到潜在的长时间暴露，这些异常需要评估。(C) 2014 S. Karger AG，巴塞尔
Background: Human deficiency virus (HIV) protease inhibitors (PIs) are widely used drugs whose effects are pharmacologically enhanced by ritonavir, a potent cytochrome P450 inhibitor. We reported previously that prophylactic postnatal ritonavir-PI therapy in HIV-exposed neonates was associated with increases in plasma 17-hydroxyprogesterone (17-OHP) and dehydroepiandrosterone sulfate (DHEA-S). Aims: To further investigate adrenal function in neonates and adolescents given ritonavir-PI. Methods: Adrenal function was assessed prospectively in 3 HIV-exposed neonates given short-term prophylactic treatment and 3 HIV-infected adolescents given long-term treatment. Plasma cortisol, 17-OHP, 17-OH-pregnenolone, DHEA-S, and androstenedione were measured before and after ACTH administration. Results: None of the patients had clinical signs of adrenal dysfunction. The only neonate exposed to ritonavir-PI in utero had up to 3-fold increases in plasma 17-OHP. Increases in 17-OH-pregnenolone of up to 3.1-fold were noted in 4 of the 6 patients, and all 6 patients had elevations in DHEA-S (up to 20.4-fold increase) and/or DHEA (up to 4.7-fold) and/or androstenedione (up to 5.2-fold). All these parameters improved after treatment completion. Conclusion: Neonates and adolescents given ritonavir-PI exhibit a similar adrenal dysfunction profile consistent with an impact on multiple adrenal enzymes. These abnormalities require evaluation, given the potentially long exposure times. (C) 2014 S. Karger AG, Basel