Safety of Perinatal Exposure to Antiretroviral Medications: Developmental Outcomes in Infants

Overview

Journal Pediatr Infect Dis J

Specialty Pediatrics

Date 2013 Jan 24

PMID 23340561

Citations 37

Authors

Patricia A Sirois

Yanling Huo

Paige L Williams

Kathleen Malee

Patricia A Garvie

Betsy Kammerer

Kenneth Rich

Russell B Van Dyke

Molly L Nozyce

Affiliations

Soon will be listed here.

Abstract

Background: This study evaluated effects of perinatal exposure to antiretroviral (ARV) medications on neurodevelopment of HIV-exposed, uninfected infants.

Methods: HIV-exposed, uninfected infants (age 9-15 months) enrolled in Surveillance Monitoring for Antiretroviral Therapy Toxicities, a multisite prospective surveillance study, completed the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III), assessing cognition, language, motor skills, social-emotional development and adaptive behavior. Linear regression models were used to evaluate associations between Bayley-III outcomes in infants with and without perinatal and neonatal ARV exposure, by regimen (combination ARV [cARV] versus non-cARV), type of regimen (defined by drug class) and individual ARVs (for infants with cARV exposure), adjusting for maternal and infant health and demographic covariates.

Results: As of May 2010, 374 infants had valid Bayley-III evaluations. Median age at testing was 12.7 months; 49% male, 79% black and 16% Hispanic. Seventy-nine percent were exposed to regimens containing protease inhibitors (9% of protease inhibitor-containing regimens also included non-nucleoside reverse transcriptase inhibitors), 5% to regimens containing non-nucleoside reverse transcriptase inhibitors (without protease inhibitor) and 14% to regimens containing only nucleoside reverse transcriptase inhibitors. Overall, 83% were exposed to cARV. No Bayley-III outcome was significantly associated with overall exposure to cARV, ARV regimen or neonatal prophylaxis. For individual ARVs, following sensitivity analyses, the adjusted group mean on the Language domain was within age expectations but significantly lower for infants with perinatal exposure to atazanavir (P = 0.01).

Conclusions: These results support the safety of perinatal ARV use. Continued monitoring for adverse neurodevelopmental outcomes in older children is warranted, and the safety of atazanavir merits further study.

Citing Articles

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Perinatal exposure to atazanavir-based antiretroviral regimens in a mouse model leads to differential long-term motor and cognitive deficits dependent on the NRTI backbone.

Dhume S, Balogun K, Sarkar A, Acosta S, Mount H, Cahill L Front Mol Neurosci. 2024; 17:1376681.

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References

Williams P, Marino M, Malee K, Brogly S, Hughes M, Mofenson L . Neurodevelopment and in utero antiretroviral exposure of HIV-exposed uninfected infants. Pediatrics. 2010; 125(2):e250-60. PMC: 2951128. DOI: 10.1542/peds.2009-1112. View

Brogly S, DiMauro S, Van Dyke R, Williams P, Naini A, Libutti D . Short communication: transplacental nucleoside analogue exposure and mitochondrial parameters in HIV-uninfected children. AIDS Res Hum Retroviruses. 2010; 27(7):777-83. PMC: 3159117. DOI: 10.1089/aid.2010.0204. View

Mandelbrot L, Mazy F, Floch-Tudal C, Meier F, Azria E, Crenn-Hebert C . Atazanavir in pregnancy: impact on neonatal hyperbilirubinemia. Eur J Obstet Gynecol Reprod Biol. 2011; 157(1):18-21. DOI: 10.1016/j.ejogrb.2011.02.005. View

Heidari S, Mofenson L, Cotton M, Marlink R, Cahn P, Katabira E . Antiretroviral drugs for preventing mother-to-child transmission of HIV: a review of potential effects on HIV-exposed but uninfected children. J Acquir Immune Defic Syndr. 2011; 57(4):290-6. DOI: 10.1097/QAI.0b013e318221c56a. View

Venerosi A, Cirulli F, Lilp I, Fiore M, Calamandrei G, Alleva E . Prolonged perinatal exposure to AZT affects aggressive behaviour of adult CD-1 mice. Psychopharmacology (Berl). 2000; 150(4):404-11. DOI: 10.1007/s002130000455. View

Whitmore S, Zhang X, Taylor A, Blair J . Estimated number of infants born to HIV-infected women in the United States and five dependent areas, 2006. J Acquir Immune Defic Syndr. 2011; 57(3):218-22. DOI: 10.1097/QAI.0b013e3182167dec. View

Venerosi A, Valanzano A, Puopolo M, Calamandrei G . Neurobehavioral effects of prenatal exposure to AZT: a preliminary investigation with the D1 receptor agonist SKF 38393 in mice. Neurotoxicol Teratol. 2005; 27(1):169-73. DOI: 10.1016/j.ntt.2004.09.008. View

Venerosi A, Calamandrei G, Alleva E . Animal models of anti-HIV drugs exposure during pregnancy: effects on neurobehavioral development. Prog Neuropsychopharmacol Biol Psychiatry. 2002; 26(4):747-61. DOI: 10.1016/s0278-5846(01)00325-6. View

Thorne C, Newell M . Safety of agents used to prevent mother-to-child transmission of HIV: is there any cause for concern?. Drug Saf. 2007; 30(3):203-13. DOI: 10.2165/00002018-200730030-00004. View

10.

Schuler M, Nair P, Harrington D . Developmental outcome of drug-exposed children through 30 months: a comparison of Bayley and Bayley-II. Psychol Assess. 2003; 15(3):435-8. DOI: 10.1037/1040-3590.15.3.435. View

11.

Connor E, Sperling R, Gelber R, Kiselev P, Scott G, OSullivan M . Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med. 1994; 331(18):1173-80. DOI: 10.1056/NEJM199411033311801. View

12.

Rondinini C, Venerosi A, Branchi I, Calamandrei G, Alleva E . Long-term effects of prenatal 3'-azido-3'-deoxythymidine (AZT) exposure on intermale aggressive behaviour of mice. Psychopharmacology (Berl). 1999; 145(3):317-23. DOI: 10.1007/s002130051064. View

13.

Griner R, Williams P, Read J, Seage 3rd G, Crain M, Yogev R . In utero and postnatal exposure to antiretrovirals among HIV-exposed but uninfected children in the United States. AIDS Patient Care STDS. 2011; 25(7):385-94. PMC: 3125552. DOI: 10.1089/apc.2011.0068. View

14.

Ivanovic J, Nicastri E, Anceschi M, Ascenzi P, Signore F, Pisani G . Transplacental transfer of antiretroviral drugs and newborn birth weight in HIV-infected pregnant women. Curr HIV Res. 2009; 7(6):620-5. DOI: 10.2174/157016209789973628. View

15.

Poirier M, Olivero O, Walker D, Walker V . Perinatal genotoxicity and carcinogenicity of anti-retroviral nucleoside analog drugs. Toxicol Appl Pharmacol. 2004; 199(2):151-61. DOI: 10.1016/j.taap.2003.11.034. View

16.

Malee K, Tassiopoulos K, Huo Y, Siberry G, Williams P, Hazra R . Mental health functioning among children and adolescents with perinatal HIV infection and perinatal HIV exposure. AIDS Care. 2011; 23(12):1533-44. PMC: 3387978. DOI: 10.1080/09540121.2011.575120. View

17.

Calamandrei G, Valanzano A, Puopolo M, Aloe L . Developmental exposure to the antiretroviral drug zidovudine increases brain levels of brain-derived neurotrophic factor in mice. Neurosci Lett. 2002; 333(2):111-4. DOI: 10.1016/s0304-3940(02)01023-6. View

18.

Culnane M, Fowler M, Lee S, McSherry G, Brady M, ODonnell K . Lack of long-term effects of in utero exposure to zidovudine among uninfected children born to HIV-infected women. Pediatric AIDS Clinical Trials Group Protocol 219/076 Teams. JAMA. 1999; 281(2):151-7. DOI: 10.1001/jama.281.2.151. View

19.

Fundaro C, Genovese O, Rendeli C, Tamburrini E, Salvaggio E . Myelomeningocele in a child with intrauterine exposure to efavirenz. AIDS. 2002; 16(2):299-300. DOI: 10.1097/00002030-200201250-00025. View

20.

Bradley R, Corwyn R . Socioeconomic status and child development. Annu Rev Psychol. 2001; 53:371-99. DOI: 10.1146/annurev.psych.53.100901.135233. View