In utero exposure to zidovudine and heart anomalies in the ANRS French perinatal cohort and the nested PRIMEVA randomized trial.

Autor:	Sibiude J; Department of Obstetrics and Gynecology, Hôpital Louis Mourier, Colombes Department of Epidemiology, Centre de Recherche en Épidémiologie et Santé des Populations, Institut National de la Santé et de la Recherche Médicale (INSERM) U1018, Le Kremlin-Bicêtre., Le Chenadec J; Department of Epidemiology, Centre de Recherche en Épidémiologie et Santé des Populations, Institut National de la Santé et de la Recherche Médicale (INSERM) U1018, Le Kremlin-Bicêtre., Bonnet D; M3C-Pediatric Cardiology, Assistance Publique, Hôpitaux de Paris (APHP) Hôpital Necker Enfants malades, Université Paris Descartes., Tubiana R; Department of Infectiology, AP-HP, GH Pitié-Salpêtrière, Pierre Louis Institute of Epidemiology and Public Health, Sorbonne University, UPMC, INSERM UMR-S1136., Faye A; Department of Pediatrics, AP-HP Hôpital Robert Debré Université Diderot Paris 7., Dollfus C; Department of Pediatrics AP-HP Hôpital Trousseau., Mandelbrot L; Department of Obstetrics and Gynecology, Hôpital Louis Mourier, Colombes Department of Epidemiology, Centre de Recherche en Épidémiologie et Santé des Populations, Institut National de la Santé et de la Recherche Médicale (INSERM) U1018, Le Kremlin-Bicêtre Université Diderot Paris 7., Delmas S; Department of Epidemiology, Centre de Recherche en Épidémiologie et Santé des Populations, Institut National de la Santé et de la Recherche Médicale (INSERM) U1018, Le Kremlin-Bicêtre., Lelong N; INSERM, UMR S953, Université Paris-6., Khoshnood B; INSERM, UMR S953, Université Paris-6., Warszawski J; Department of Epidemiology, Centre de Recherche en Épidémiologie et Santé des Populations, Institut National de la Santé et de la Recherche Médicale (INSERM) U1018, Le Kremlin-Bicêtre Institut National d'études Démographiques, Paris Université Paris Sud, Le Kremlin-Bicêtre., Blanche S; Department of Pediatrics, Hôpital Necker EA 7223: Évaluation Thérapeutique et Pharmacologie Périnatale et Pédiatrique, Université Paris Descartes, France.
Jazyk:	angličtina
Zdroj:	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2015 Jul 15; Vol. 61 (2), pp. 270-80. Date of Electronic Publication: 2015 Apr 01.
DOI:	10.1093/cid/civ260
Abstrakt:	Background: Antiretroviral (ARV) regimens during pregnancy are highly effective in preventing mother-to-child transmission of human immunodeficiency virus (HIV). Congenital heart defects (CHDs) and anomalies in cardiac function have been reported in zidovudine (ZDV)-exposed uninfected children. We explored these associations in a large observational cohort and a randomized clinical trial. Methods: Since 1986, the French Perinatal Cohort prospectively enrolled all HIV-infected women in 90 centers and collected follow-up on their children through 2 years of age. All CHDs were reviewed by a specialist blinded to exposures. Additionally, in a randomized trial (PRIMEVA ANRS 135) of 2 ARV regimens during pregnancy, 1 of which was without nucleoside reverse transcriptase inhibitors, infants had a specific follow-up including echocardiography at 1 month and 12 months. Results: Among 12 888 children included, ZDV exposure in the first trimester was significantly associated with CHD (1.5% vs 0.7%; adjusted odds ratio, 2.2 [95% confidence interval, 1.3-3.7]; P < .001). This association was significant for ventricular septal defects (1.1% vs 0.6%; P = .001) and other CHDs (0.31% vs 0.11%; P = .02). In the randomized trial, among 50 infants, girls (but not boys) exposed in utero to ZDV/lamivudine/ritonavir-boosted lopinavir (LPV/r) had a higher left ventricular shortening fraction at 1 month (40% vs 36%; P = .008), and an increased posterior wall thickness at 1 year (5.4 mm vs 4.4 mm; P = .01) than the LPV/r group. Conclusions: This study confirms a specific association between in utero exposure to ZDV and CHDs, and a long-lasting postnatal myocardial remodeling in girls. A potential common mechanism, including the involvement of mitochondrial dysfunction, must be explored, and long-term consequences on cardiac function warrant specific attention. Clinical Trials Registration: NCT00424814. (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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