title: Association of prenatal and postnatal exposure to lopinavir-ritonavir and adrenal dysfunction among uninfected infants of HIV-infected mothers.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To evaluate adrenal function in newborns postnatally treated with lopinavir-ritonavir.
  
  
  METHODS
  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.
  
  
  METHODS
  Plasma 17OHP and dehydroepiandrosterone-sulfate (DHEA-S) concentrations during the first week of treatment. Clinical and biological symptoms compatible with adrenal deficiency.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Unité d’Endocrinologie Pédiatrique, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors: Albane
authors: A
authors: Simon
authors: Josiane
authors: J
authors: Warszawski
authors: Dulanjalee
authors: D
authors: Kariyawasam
authors: Jerome
authors: J
authors: Le Chenadec
authors: Valerie
authors: V
authors: Benhammou
authors: Paul
authors: P
authors: Czernichow
authors: Frantz
authors: F
authors: Foissac
authors: Kathleen
authors: K
authors: Laborde
authors: Jean-Marc
authors: JM
authors: Tréluyer
authors: Ghislaine
authors: G
authors: Firtion
authors: Inès
authors: I
authors: Layouni
authors: Martine
authors: M
authors: Munzer
authors: Françoise
authors: F
authors: Bavoux
authors: Michel
authors: M
authors: Polak
authors: Stéphane
authors: S
authors: Blanche
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000309:Adrenal Insufficiency / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D005260:Female; D005602:France / Q000453:epidemiology; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control / Q000635:transmission*; D015497:HIV-1; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D061466:Lopinavir; D008297:Male; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy / Q000517:prevention & control*; D011744:Pyrimidinones / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects*; D015215:Zidovudine / Q000008:administration & dosage
chemical_list: D011744:Pyrimidinones; D061466:Lopinavir; D015215:Zidovudine; D019314:Dehydroepiandrosterone Sulfate; D019326:17-alpha-Hydroxyprogesterone; D019438:Ritonavir