16th International AIDS Conference Toronto, Canada - August 13 - 18, 2006

IN UTERO NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR EXPOSURE AND SIGNS OF POSSIBLE MITOCHONDRIAL DYSFUNCTION IN HIV-UNINFECTED CHILDREN IN THE PEDIATRIC AIDS CLINICAL TRIALS GROUP PROTOCOLS 219 & 219C

Int Conf AIDS. 2006 Aug 13-18;16 Abstract No. ThAb0103

Brogly S.¹, Ylitalo N.², Mofenson L.³, Oleske J.⁴, Van Dyke R.⁵, Crain M.⁶, Abzug M.⁷, Brady M.⁸, Patrick J.-P.⁹, Hughes M.¹⁰, Seage III G.R.^2
1 Harvard University, School of Public Health, Center for Biostatistics in AIDS Research, Boston, United States, ² Harvard University, School of Public Health, Department of Epidemiology, Boston, United States, ³ National Institute of Child Health & Human Development, Pediatric, Adolescent, and Maternal AIDS Branch, Rockville, United States, ⁴ University of Medicine & Dentistry of New Jersey, Department of Pediatrics, Newark, United States, ⁵ Tulane University Health Science Center, Department of Pediatrics, New Orleans, United States, ⁶ University of Alabama at Birmingham, Department of Pediatrics (Infectious Diseases), Birmingham, United States, ⁷ University of Colorado School of Medicine and the Children's Hospital, Department of Pediatrics (infectious Diseases), Denver, United States, ⁸ Children's Hospital Columbus, Department of Infectious Diseases, Columbus, United States, ⁹ National Institute of Allergy and Infectious Diseases, Bethesda, United States, ¹⁰ Harvard University, School of Public Health, Department of Biostatistics, Boston, United States

BACKGROUND: There is equivocal evidence regarding in utero nucleoside reverse transcriptase inhibitor (NRTI) exposure and mitochondrial dysfunction (MD) in HIV-uninfected children born of HIV-infected women.

METHODS: The primary analysis included 1,020 HIV-uninfected children born in 1991 to 2002 and enrolled in PACTG protocols 219 and 219C. Possible cases with unexplained signs that could be consistent with MD according to the Enquête Périnatale Française criteria were identified through retrospective review of clinical data without knowledge of in utero exposures. The association between 1) overall in utero NRTI exposure (i.e., at any time during gestation) and 2) trimester of first in utero NRTI exposure and possible MD was estimated with exact logistic regression adjusting for potential confounders.

RESULTS: Cases (N=20) were significantly more likely to be male and were born in earlier years than non-cases (N=1,000). There was no significant association between overall in utero NRTI exposure and possible MD. In unadjusted analyses, there were non-significant higher odds of first in utero exposure in the 3rd trimester to 3TC (OR=2.94 vs. unexposed, 95% CI: 0.78 – 9.49) and to ZDV/3TC in combination (OR=2.65 vs. unexposed, 95% CI: 0.71 – 8.50) among cases than non-cases. When adjusted for year of birth, the odds of first exposure in the 3rd trimester to 3TC (OR=6.27 vs. unexposed, 95% CI: 1.20 – 35.81) and to ZDV/3TC (OR=5.90 vs. unexposed, 95% CI: 1.12 – 33.98) were significantly higher among cases than non-cases. Missing data precluded adequate control of possible confounding by peak maternal viral load in the 3rd trimester and in utero psychoactive drug exposure.

CONCLUSIONS: There was no association between overall in utero NRTI exposure and possible MD. The association with first in utero exposure to 3TC and to ZDV/3TC in the 3rd trimester warrants investigation in studies that rigorously assess MD and achieve better control of confounding.

Download PDF of this abstract.

Download Power Point Presentation.

2006-08-13
ThAb0103

Copyright © 2006 - International AIDS Society (IAS). All information and content relating to the abstracts from the 16th International AIDS Conference, such as text, graphics, logos, button icons, images, audio clips, and software is protected by copyright. Permission is hereby granted for the non-commercial use or reproduction of the information on this web site, provided that the use of such information is accompanied by an acknowledgement that IAS is the source of the information and the name of the author of the article.

AEGiS is a 501c(3) not-for-profit organization made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, GlaxoSmithKline, the National Library of Medicine, Roche / Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 2006. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2006. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. Permission is hereby granted for the non-commercial use or reproduction of the information herein, provided that the use of such information is accompanied by an acknowledgement that IAS is the source of the information and the name of the author of the article.