Unité d’Endocrinologie Pédiatrique, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France.
JAMA. 2011 Jul 6;306(1):70-8. doi: 10.1001/jama.2011.915.
Lopinavir-ritonavir is a human immunodeficiency virus 1 (HIV-1) protease inhibitor boosted by ritonavir, a cytochrome p450 inhibitor. A warning about its tolerance in premature newborns was recently released, and transient elevation of 17-hydroxyprogesterone (17OHP) was noted in 2 newborns treated with lopinavir-ritonavir in France.
To evaluate adrenal function in newborns postnatally treated with lopinavir-ritonavir.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective cross-sectional analysis of the database from the national screening for congenital adrenal hyperplasia (CAH) and the French Perinatal Cohort. Comparison of HIV-1-uninfected newborns postnatally treated with lopinavir-ritonavir and controls treated with standard zidovudine.
Plasma 17OHP and dehydroepiandrosterone-sulfate (DHEA-S) concentrations during the first week of treatment. Clinical and biological symptoms compatible with adrenal deficiency.
Of 50 HIV-1-uninfected newborns who received lopinavir-ritonavir at birth for a median of 30 days (interquartile range [IQR], 25-33), 7 (14%) had elevated 17OHP levels greater than 16.5 ng/mL for term infants (>23.1 ng/mL for preterm) on days 1 to 6 vs 0 of 108 controls having elevated levels. The median 17OHP concentration for 42 term newborns treated with lopinavir-ritonavir was 9.9 ng/mL (IQR, 3.9-14.1 ng/mL) vs 3.7 ng/mL (IQR, 2.6-5.3 ng/mL) for 93 term controls (P < .001). The difference observed in median 17OHP values between treated newborns and controls was higher in children also exposed in utero (11.5 ng/mL vs 3.7 ng/mL; P < .001) than not exposed in utero (6.9 ng/mL vs 3.3 ng/mL; P = .03). The median DHEA-S concentration among 18 term newborns treated with lopinavir-ritonavir was 9242 ng/mL (IQR, 1347-25,986 ng/mL) compared with 484 ng/mL (IQR, 218-1308 ng/mL) among 17 term controls (P < .001). The 17OHP and DHEA-S concentrations were positively correlated (r = 0.53; P = .001). All term newborns treated with lopinavir-ritonavir were asymptomatic, although 3 premature newborns experienced life-threatening symptoms compatible with adrenal insufficiency, including hyponatremia and hyperkalemia with, in 1 case, cardiogenic shock. All symptoms resolved following completion of the lopinavir-ritonavir treatment.
Among newborn children of HIV-1-infected mothers exposed in utero to lopinavir-ritonavir, postnatal treatment with a lopinavir-ritonavir-based regimen, compared with a zidovudine-based regimen, was associated with transient adrenal dysfunction.
洛匹那韦/利托那韦是一种人类免疫缺陷病毒 1（HIV-1）蛋白酶抑制剂，由细胞色素 P450 抑制剂利托那韦增强。最近发布了一项关于其在早产儿中耐受性的警告，并在法国接受洛匹那韦/利托那韦治疗的 2 名新生儿中注意到 17-羟孕酮（17OHP）短暂升高。
评估新生儿在接受洛匹那韦/利托那韦治疗后的肾上腺功能。
设计、地点和参与者：回顾性分析国家先天性肾上腺增生症（CAH）筛查数据库和法国围产期队列的数据库。将接受洛匹那韦/利托那韦治疗的 HIV-1 未感染新生儿与接受标准齐多夫定治疗的对照组进行比较。
治疗第 1 周的血浆 17OHP 和脱氢表雄酮硫酸酯（DHEA-S）浓度。与肾上腺功能减退相符的临床和生物学症状。
在 50 名因 HIV-1 感染而在出生时接受洛匹那韦/利托那韦治疗的 HIV-1 未感染新生儿中，中位数为 30 天（四分位距[IQR]，25-33），有 7（14%）名婴儿在第 1 至 6 天的 17OHP 水平升高，大于 16.5ng/ml（早产儿大于 23.1ng/ml），而 108 名对照组中有 0 名升高。42 名足月新生儿接受洛匹那韦/利托那韦治疗的中位 17OHP 浓度为 9.9ng/ml（IQR，3.9-14.1ng/ml），93 名足月对照组为 3.7ng/ml（IQR，2.6-5.3ng/ml）（P<0.001）。在接受治疗的新生儿和对照组中，17OHP 中位数的差异在宫内暴露的儿童中（11.5ng/ml 比 3.7ng/ml；P<0.001）比未宫内暴露的儿童中（6.9ng/ml 比 3.3ng/ml；P=0.03）更高。18 名接受洛匹那韦/利托那韦治疗的足月新生儿的中位 DHEA-S 浓度为 9242ng/ml（IQR，1347-25986ng/ml），而 17 名足月对照组的中位浓度为 484ng/ml（IQR，218-1308ng/ml）（P<0.001）。17OHP 和 DHEA-S 浓度呈正相关（r=0.53；P=0.001）。所有接受洛匹那韦/利托那韦治疗的足月新生儿均无症状，但 3 名早产儿出现危及生命的肾上腺功能减退症状，包括低钠血症和高钾血症，1 例合并心源性休克。所有症状均在完成洛匹那韦/利托那韦治疗后得到缓解。
在 HIV-1 感染母亲宫内暴露于洛匹那韦/利托那韦的新生儿中，与齐多夫定相比，洛匹那韦/利托那韦的基于方案的治疗与短暂的肾上腺功能障碍相关。
