Association of prenatal and postnatal exposure to lopinavir-ritonavir and adrenal dysfunction among uninfected infants of HIV-infected mothers
| Autor: | Albane Simon, Josiane Warszawski, Dulanjalee Kariyawasam, Jerome Le Chenadec, Valerie Benhammou, Paul Czernichow, Frantz Foissac, Kathleen Laborde, Jean-Marc Tréluyer, Ghislaine Firtion, Inès Layouni, Martine Munzer, Françoise Bavoux, Michel Polak, Stéphane Blanche, for the ANRS French Perinatal Cohort Study Group |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty Lopinavir/ritonavir Physiology Context (language use) HIV Infections Pyrimidinones Lopinavir 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Dehydroepiandrosterone sulfate immune system diseases Interquartile range Pregnancy Internal medicine medicine Humans Congenital adrenal hyperplasia 030212 general & internal medicine Pregnancy Complications Infectious Retrospective Studies 0303 health sciences Ritonavir 030306 microbiology business.industry Dehydroepiandrosterone Sulfate 17-alpha-Hydroxyprogesterone Infant Newborn virus diseases General Medicine medicine.disease Infectious Disease Transmission Vertical 3. Good health Regimen Endocrinology Cross-Sectional Studies chemistry Case-Control Studies HIV-1 Female France business Zidovudine medicine.drug Adrenal Insufficiency |
| Zdroj: | JAMA; Vol 306 |
| ISSN: | 0098-7484 |
| DOI: | 10.1001/jama.2011.915 |
| Popis: | 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.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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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