Document Detail


Association of prenatal and postnatal exposure to lopinavir-ritonavir and adrenal dysfunction among uninfected infants of HIV-infected mothers.
MedLine Citation:
PMID:  21730243     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CONTEXT: 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.
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.
MAIN OUTCOME MEASURES: 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.
CONCLUSION: 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:
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;
Related Documents :
20478353 - Docosahexaenoic acid (dha) and the developing central nervous system (cns) - implicatio...
1877513 - Nutritional status of infants with cystic fibrosis associated with early diagnosis and ...
11531153 - The effect of variable heart rate decelerations on intraventricular hemorrhage and othe...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  JAMA     Volume:  306     ISSN:  1538-3598     ISO Abbreviation:  JAMA     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-06     Completed Date:  2011-07-07     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  7501160     Medline TA:  JAMA     Country:  United States    
Other Details:
Languages:  eng     Pagination:  70-8     Citation Subset:  AIM; IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
17-alpha-Hydroxyprogesterone / blood
Adrenal Insufficiency / blood,  chemically induced*,  epidemiology
Case-Control Studies
Cross-Sectional Studies
Dehydroepiandrosterone Sulfate / blood
Female
France / epidemiology
HIV Infections / drug therapy,  prevention & control,  transmission*
HIV-1*
Humans
Infant, Newborn
Infectious Disease Transmission, Vertical / prevention & control*
Lopinavir
Male
Pregnancy
Pregnancy Complications, Infectious / drug therapy,  prevention & control*
Pyrimidinones / administration & dosage,  adverse effects*
Retrospective Studies
Ritonavir / administration & dosage,  adverse effects*
Zidovudine / administration & dosage
Chemical
Reg. No./Substance:
0/Pyrimidinones; 2494G1JF75/Lopinavir; 4B9XT59T7S/Zidovudine; 57B09Q7FJR/Dehydroepiandrosterone Sulfate; 68-96-2/17-alpha-Hydroxyprogesterone; O3J8G9O825/Ritonavir
Investigator
Investigator/Affiliation:
N Decaux / ; Y Douadi / ; J Gondry / ; V Li Thiao Te / ; J L Schmit / ; A Fournié / ; C Allisy / ; D Brault / ; E Questiaux / ; A Zakaria / ; C Goldenstein / ; O Pincemaille / ; F Bonnal / ; C Cayla / ; X Hernandorena / ; J M Estavoyer / ; R Maillet / ; M Bentata / ; L Benoist / ; S Bolie / ; N Bonier / ; E Lachassine / ; A Rodrigues / ; D Douard / ; D Roux / ; V Schaeffer / ; G Beucher / ; J Brouard / ; P Goubin / ; N Elenga / ; P Ceccaldi-Carp / ; B Fantin / ; D Luton / ; H Pejoan / ; B Carpentier / ; M Duval-Arnould / ; C Kingue-Ekollo / ; V Garrait / ; S Lemerle / ; C Pichon / ; C Richier / ; C Touboul / ; D Bornarel / ; V Chambrin / ; L Clech / ; L Foix L'Hélias / ; P Labrune / ; H Schoen / ; C Crenn-Hebert / ; C Floch-Tudal / ; F Mazy / ; E Hery / ; C Meier / ; S Martha / ; I Reynaud / ; C Allouche / ; K Touré / ; P Chevojon / ; A Devidas / ; M Granier / ; C Marchand / ; A May / ; R Nguyen / ; I Turpault / ; K Alissa / ; C Routier / ; Y Hatchuel / ; C William / ; T Jault / ; I Jrad / ; A Chalvon Demersay / ; E Froguel / ; B Gourdel / ; C Lanty / ; O Aubry / ; J P Brossier / ; J L Esnault / ; S Leautez / ; P Perré / ; I Suaud / ; J M Chamouilli / ; V Hentgen / ; F Messaoudi / ; C Colmant / ; C Fourcade / ; S Fridman / ; D Peretti / ; S D'angelo / ; Y Hammou / ; F Mazingue / ; P Bailly-Salin / ; I Turpault / ; H Seaume / ; C Brochier / ; L Cotte / ; J M Labaune / ; T Le Thi / ; M J Roussouly / ; O Tariel / ; V Thoirain / ; Y Bertrand / ; K Kebaïli / ; N Tache / ; J Massardier / ; A Delanete / ; A Doumet / ; F Granier / ; J L Salomon / ; L Cravello / ; I Thuret / ; L Karaoui / ; V Lefèvre / ; B Le Lorier / ; M Dehlinger / ; M Echard / ; C Mullard / ; P Talon / ; P Benos / ; N Guigue / ; M Lalande / ; B Heller-Roussin / ; C Riehl / ; C Winter / ; C Hubert / ; C Brunet-François / ; Mechinaud / ; V Reliquet / ; A Bongain / ; A Deville / ; E Galiba / ; F Monpoux / ; J Dendale-Nguyen / ; P Arsac / ; E Werner / ; S Chanzy / ; C De Gennes / ; V Isart / ; H Bastian / ; A Bourgeois-Moine / ; S Matheron / ; R Rajguru / ; N Boudjoudi / ; G Firtion / ; M Fouchet / ; I Goupil / ; A Pannier / ; D Ayral / ; N Ciraru-Vigneron / ; G Mouchnino / ; S Boucly / ; S Blanche / ; A Maignan / ; S Parat / ; C Rouzioux / ; J P Viard / ; A Yamgnane / ; V Cayol / ; M Bonmarchand / ; I De Montgolfier / ; F Quetin / ; N Edeb / ; D Lemercier / ; M Harif / ; A Naime-Alix / ; M Pauchard / ; R Tubiana / ; A De Lauzanne / ; A Faye / ; D Garion / ; S Leveille / ; M Levine / ; A Ottenwalter / ; A Recoules / ; E Bui / ; B Carbonne / ; M C Meyohas / ; J Rodriguez / ; C Aufrant / ; F Hervé / ; M G Lebrette / ; C Dollfus / ; M D Tabone / ; G Vaudre / ; A Wallet / ; G Bachelard / ; M Medus / ; H Bataille / ; A Coursol / ; M Munzer / ; V Brossard / ; M C Allemon / ; P Bolot / ; D Ekoukou / ; N Ghibaudo / ; S Gyardeau / ; M A Khuong / ; K Billiemaz / ; F Bissuel / ; V Walter / ; M Cheneau / ; N Entz-Werle / ; J Favreau / ; M Partisani / ; G Hittinger / ; M Antras / ; E Armand / ; A Berrebi / ; J Tricoire / ; J M Besnier / ; P Nau / ; L Neimann / ; A Chacé / ; F Guillot / ; I Matheron /

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Adherence to a low-risk, healthy lifestyle and risk of sudden cardiac death among women.
Next Document:  The development of an adolescent smoking cessation intervention--an Intervention Mapping approach to...