Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
JAMA. 2011 Jul 6;306(1):70-8. doi: 10.1001/jama.2011.915.

Association of prenatal and postnatal exposure to lopinavir-ritonavir and adrenal dysfunction among uninfected infants of HIV-infected mothers.

Collaborators (214)

Decaux N, Douadi Y, Gondry J, Li Thiao Te V, Schmit JL, Fournié A, Allisy C, Brault D, Questiaux E, Zakaria A, Goldenstein C, Pincemaille O, Bonnal F, Cayla C, Hernandorena X, Estavoyer JM, Maillet R, Bentata M, Benoist L, Bolie S, Bonier N, Lachassine E, Rodrigues A, Douard D, Roux D, Schaeffer V, Beucher G, Brouard J, Goubin P, Elenga N, Ceccaldi-Carp P, Fantin B, Luton D, Pejoan H, Carpentier B, Duval-Arnould M, Kingue-Ekollo C, Garrait V, Lemerle S, Pichon C, Richier C, Touboul C, Bornarel D, Chambrin V, Clech L, Foix L'Hélias L, Labrune P, Schoen H, Crenn-Hebert C, Floch-Tudal C, Mazy F, Hery E, Meier C, Martha S, Reynaud I, Allouche C, Touré K, Chevojon P, Devidas A, Granier M, Marchand C, May A, Nguyen R, Turpault I, Alissa K, Routier C, Hatchuel Y, William C, Jault T, Jrad I, Chalvon Demersay A, Froguel E, Gourdel B, Lanty C, Aubry O, Brossier JP, Esnault JL, Leautez S, Perré P, Suaud I, Chamouilli JM, Hentgen V, Messaoudi F, Colmant C, Fourcade C, Fridman S, Peretti D, D'angelo S, Hammou Y, Mazingue F, Bailly-Salin P, Turpault I, Seaume H, Brochier C, Cotte L, Labaune JM, Le Thi T, Roussouly MJ, Tariel O, Thoirain V, Bertrand Y, Kebaïli K, Tache N, Massardier J, Delanete A, Doumet A, Granier F, Salomon JL, Cravello L, Thuret I, Karaoui L, Lefèvre V, Le Lorier B, Dehlinger M, Echard M, Mullard C, Talon P, Benos P, Guigue N, Lalande M, Heller-Roussin B, Riehl C, Winter C, Hubert C, Brunet-François C, Mechinaud, Reliquet V, Bongain A, Deville A, Galiba E, Monpoux F, Dendale-Nguyen J, Arsac P, Werner E, Chanzy S, De Gennes C, Isart V, Bastian H, Bourgeois-Moine A, Matheron S, Rajguru R, Boudjoudi N, Firtion G, Fouchet M, Goupil I, Pannier A, Ayral D, Ciraru-Vigneron N, Mouchnino G, Boucly S, Blanche S, Maignan A, Parat S, Rouzioux C, Viard JP, Yamgnane A, Cayol V, Bonmarchand M, De Montgolfier I, Quetin F, Edeb N, Lemercier D, Harif M, Naime-Alix A, Pauchard M, Tubiana R, De Lauzanne A, Faye A, Garion D, Leveille S, Levine M, Ottenwalter A, Recoules A, Bui E, Carbonne B, Meyohas MC, Rodriguez J, Aufrant C, Hervé F, Lebrette MG, Dollfus C, Tabone MD, Vaudre G, Wallet A, Bachelard G, Medus M, Bataille H, Coursol A, Munzer M, Brossard V, Allemon MC, Bolot P, Ekoukou D, Ghibaudo N, Gyardeau S, Khuong MA, Billiemaz K, Bissuel F, Walter V, Cheneau M, Entz-Werle N, Favreau J, Partisani M, Hittinger G, Antras M, Armand E, Berrebi A, Tricoire J, Besnier JM, Nau P, Neimann L, Chacé A, Guillot F, Matheron I.

Author information

  • 1Unité d’Endocrinologie Pédiatrique, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France.

Abstract

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.

PMID:
21730243
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Silverchair Information Systems
    Loading ...
    Write to the Help Desk