Skip to main content
Top
Published in: European Journal of Pediatrics 7/2016

01-07-2016 | Short Communication

Influence of new antiretrovirals on hematological toxicity in HIV-exposed uninfected infants

Authors: Núria Rovira, Antoni Noguera-Julian, Susana Rives, Rubén Berrueco, Rebeca Lahoz, Clàudia Fortuny

Published in: European Journal of Pediatrics | Issue 7/2016

Login to get access

Abstract

Maternal combined antiretroviral therapy (cART) successfully prevents HIV mother-to-child transmission but also causes hematological toxicity in the HIV-exposed uninfected (HEU) infant. We performed a single-center prospective observational study. Hematological toxicity during the first year of life (at 3 and 6 weeks, and 3, 6, and 12 months) was compared between HEU infants born in two different time periods: P1 (2000–2001) and P2 (2007–2013). Mother-infant pairs in P1 (n = 55) and P2 (n = 48) mainly differed in maternal ethnic origin, HIV route of transmission, and cART regimens. Anemia and neutropenia were both less common in P2 than P1, albeit not significantly. Earlier normalization of red blood cell mean corpuscular volume levels in P2 infants suggests that current cART maternal regimens and shorter neonatal prophylaxis are less toxic. Leukocyte, lymphocyte, and platelet counts remained within normal values during follow-up, without differences between groups.
Conclusion: New cART regimens have had very little impact on the hematological toxicity in HEU infants.
What is Known:
Antiretroviral drugs during pregnancy and the neonatal period very effectively prevent mother-to-child transmission of HIV infection.
Hematological toxicity has been widely reported among HIV-exposed uninfected children.
What is New:
In HIV-exposed uninfected children, hematological toxicity is still mainly caused by exposure to zidovudine.
New antiretroviral drugs have very little impact on hematological toxicity among HIV-exposed uninfected children.
Literature
1.
go back to reference Bridges EG, Trentesaux C, Lahlil R, Spiga MG, Jeannesson P, Sommadossi JP (1996) 3′-Azido-3′-deoxythymidine inhibits erytroid- specific transcription factors in human erythroid K562 leukemia cells. Eur J Haematol 56:62–67CrossRefPubMed Bridges EG, Trentesaux C, Lahlil R, Spiga MG, Jeannesson P, Sommadossi JP (1996) 3′-Azido-3′-deoxythymidine inhibits erytroid- specific transcription factors in human erythroid K562 leukemia cells. Eur J Haematol 56:62–67CrossRefPubMed
2.
go back to reference Bunders MJ, Bekker V, Scherpbier J, Boer K, Godfried M, Kuijpers TW (2005) Haematological parameters of HIV-1-uninfected infants born to HIV-1-infected mothers. Acta Paediatr 94:1571–1577CrossRefPubMed Bunders MJ, Bekker V, Scherpbier J, Boer K, Godfried M, Kuijpers TW (2005) Haematological parameters of HIV-1-uninfected infants born to HIV-1-infected mothers. Acta Paediatr 94:1571–1577CrossRefPubMed
3.
go back to reference Connor E, Sperling R, Gelber R, Kiselev P, Scott G, O’Sullivan M, VanDyke R, Bey M, Shearer W, Jacobson R et al (1994) Reduction of maternal infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. N Engl J Med 331:1173–1180CrossRefPubMed Connor E, Sperling R, Gelber R, Kiselev P, Scott G, O’Sullivan M, VanDyke R, Bey M, Shearer W, Jacobson R et al (1994) Reduction of maternal infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. N Engl J Med 331:1173–1180CrossRefPubMed
4.
go back to reference Dainiak N, Worthington M, Riordan MA, Kreczko S, Goldman L (1988) 3′-Azido-3′-deoxythymidine (AZT) inhibits proliferation in vitro of human haematopoietic progenitor cells. Br J Haematol 69:299–304CrossRefPubMed Dainiak N, Worthington M, Riordan MA, Kreczko S, Goldman L (1988) 3′-Azido-3′-deoxythymidine (AZT) inhibits proliferation in vitro of human haematopoietic progenitor cells. Br J Haematol 69:299–304CrossRefPubMed
5.
go back to reference Dryden-Peterson S, Shapiro RL, Hughes MD, Powis K, Ogwu A, Moffat C, Moyo S, Makhema J, Essex M, Lockman S (2011) Increased risk of severe infant anemia after exposure to maternal HAART, Botswana. J Acquir Immune Defic Syndr 56:428–436CrossRefPubMedPubMedCentral Dryden-Peterson S, Shapiro RL, Hughes MD, Powis K, Ogwu A, Moffat C, Moyo S, Makhema J, Essex M, Lockman S (2011) Increased risk of severe infant anemia after exposure to maternal HAART, Botswana. J Acquir Immune Defic Syndr 56:428–436CrossRefPubMedPubMedCentral
6.
go back to reference Gogu SR, Malter JS, Agrawal KC (1992) Zidovudine-induced blockade of the expression and function of the erythropoietin receptor. Biochem Pharmacol 44:1009–1012CrossRefPubMed Gogu SR, Malter JS, Agrawal KC (1992) Zidovudine-induced blockade of the expression and function of the erythropoietin receptor. Biochem Pharmacol 44:1009–1012CrossRefPubMed
8.
go back to reference Jones CE, Naidoo S, De Beer C, Esser M, Kampmann B, Hesseling AC (2011) Maternal HIV infection and antibody responses against vaccine-preventable diseases in uninfected infants. J Am Med Assoc 305:576–584CrossRef Jones CE, Naidoo S, De Beer C, Esser M, Kampmann B, Hesseling AC (2011) Maternal HIV infection and antibody responses against vaccine-preventable diseases in uninfected infants. J Am Med Assoc 305:576–584CrossRef
9.
go back to reference Lahoz R, Noguera A, Rovira N, Català A, Sánchez E, Jimenez R, Fortuny C (2010) Antiretroviral-related hematologic short-term toxicity in healthy infants. Implications of the new neonatal 4-week zidovudine regimen. Pediatr Infect Dis J 29:376–379PubMed Lahoz R, Noguera A, Rovira N, Català A, Sánchez E, Jimenez R, Fortuny C (2010) Antiretroviral-related hematologic short-term toxicity in healthy infants. Implications of the new neonatal 4-week zidovudine regimen. Pediatr Infect Dis J 29:376–379PubMed
10.
go back to reference Le Chenadec J, Mayaux MJ, Guihenneuc-Jouyaux C, Blanche S, Enquête Périnatale Française Study Group (2003) Perinatal antiretroviral treatment and hematopoiesis in HIV-uninfected infants. AIDS 17:2053–2061CrossRefPubMed Le Chenadec J, Mayaux MJ, Guihenneuc-Jouyaux C, Blanche S, Enquête Périnatale Française Study Group (2003) Perinatal antiretroviral treatment and hematopoiesis in HIV-uninfected infants. AIDS 17:2053–2061CrossRefPubMed
11.
go back to reference Lewis LD, Amin S, Civin CI, Letman PS (2004) Ex vivo zidovudine (AZT) treatment of CD34+ bone marrow progenitors causes decreased steady state mitochondrial DNA (mtDNA) and increased lactate production. Hum Exp Toxicol 23:173–185CrossRefPubMed Lewis LD, Amin S, Civin CI, Letman PS (2004) Ex vivo zidovudine (AZT) treatment of CD34+ bone marrow progenitors causes decreased steady state mitochondrial DNA (mtDNA) and increased lactate production. Hum Exp Toxicol 23:173–185CrossRefPubMed
13.
14.
go back to reference Sollay S, Noguera Julian A, Galli L, Fortuny C, Deyà A, de Martino M, Chiappini E (2015) Strategies for the prevention of mother to child transmission in western countries. Pediatr Infect Dis J 34:S14–S30CrossRef Sollay S, Noguera Julian A, Galli L, Fortuny C, Deyà A, de Martino M, Chiappini E (2015) Strategies for the prevention of mother to child transmission in western countries. Pediatr Infect Dis J 34:S14–S30CrossRef
15.
go back to reference Stevens GA, Finucane MM, De-Regil LM, Paciorek CJ, Flaxman SR, Branca F, Peña-Rosas JP, Bhutta ZA, Ezzati M, Nutrition Impact Model Study Group (Anaemia) (2013) Global, regional, and national trends in haemoglobin concentration and prevalence of total and severe anaemia in children and pregnant and non-pregnant women for 1995–2011: a systematic analysis of population-representative data. Lancet Glob Health 1:e16–e25CrossRefPubMedPubMedCentral Stevens GA, Finucane MM, De-Regil LM, Paciorek CJ, Flaxman SR, Branca F, Peña-Rosas JP, Bhutta ZA, Ezzati M, Nutrition Impact Model Study Group (Anaemia) (2013) Global, regional, and national trends in haemoglobin concentration and prevalence of total and severe anaemia in children and pregnant and non-pregnant women for 1995–2011: a systematic analysis of population-representative data. Lancet Glob Health 1:e16–e25CrossRefPubMedPubMedCentral
16.
go back to reference Taron-Brocard C, Le Chenadec J, Faye A, Dollfus C, Goetghebuer T, Gajdos V, Labaume JM, Perilhou A, Mandelbrot L, Blanche J et al (2014) Increased risk of serious bacterial infections due to maternal immunosuppression in HIV-exposed uninfected infants in a European country. Clin Infect Dis 59:1332–1345CrossRefPubMed Taron-Brocard C, Le Chenadec J, Faye A, Dollfus C, Goetghebuer T, Gajdos V, Labaume JM, Perilhou A, Mandelbrot L, Blanche J et al (2014) Increased risk of serious bacterial infections due to maternal immunosuppression in HIV-exposed uninfected infants in a European country. Clin Infect Dis 59:1332–1345CrossRefPubMed
Metadata
Title
Influence of new antiretrovirals on hematological toxicity in HIV-exposed uninfected infants
Authors
Núria Rovira
Antoni Noguera-Julian
Susana Rives
Rubén Berrueco
Rebeca Lahoz
Clàudia Fortuny
Publication date
01-07-2016
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Pediatrics / Issue 7/2016
Print ISSN: 0340-6199
Electronic ISSN: 1432-1076
DOI
https://doi.org/10.1007/s00431-016-2730-x

Other articles of this Issue 7/2016

European Journal of Pediatrics 7/2016 Go to the issue