Skip to main content

Advertisement

SpringerLink
Log in

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

  • Short Communication
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Abbreviations

ARV:

Antiretroviral

cART:

Combined antiretroviral treatment

DAIDS:

Division of acquired immunodeficiency syndrome

HCV:

Hepatitis C virus

HIV:

Human immunodeficiency virus

MCV:

Mean corpuscular volume

MTCT:

Mother-to-child transmission

ZDV:

Zidovudine

References

  1. 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 56:62–67

    Article  CAS  PubMed  Google Scholar 

  2. 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 94:1571–1577

    Article  PubMed  Google Scholar 

  3. 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 331:1173–1180

    Article  CAS  PubMed  Google Scholar 

  4. 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 69:299–304

    Article  CAS  PubMed  Google Scholar 

  5. 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 56:428–436

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Gogu SR, Malter JS, Agrawal KC (1992) Zidovudine-induced blockade of the expression and function of the erythropoietin receptor. Biochem Pharmacol 44:1009–1012

    Article  CAS  PubMed  Google Scholar 

  7. Grupo de expertos de la Secretaría del Plan Nacional sobre el Sida (SPNS), Grupo de Estudio de Sida (GeSIDA)/Sociedad Española de Ginecología y Obstetricia (SEGO) y Sociedad Española de Infectología Pediátrica (SEIP) (2013) Documento de consenso para el seguimiento de la infección por el VIH en relación con la reproducción, embarazo, parto y profilaxis de la transmision vertical del niño expuesto. Available at: http://www.msssi.gob.es/ciudadanos/enfLesiones/enfTransmisibles/sida/publicaciones/profSanitarios/DocEmbarazoMarzo2013.pdf. Accessed 3 Dec 2015

  8. 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 305:576–584

    Article  CAS  Google Scholar 

  9. 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 29:376–379

    PubMed  Google Scholar 

  10. 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 17:2053–2061

    Article  PubMed  Google Scholar 

  11. 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 23:173–185

    Article  CAS  PubMed  Google Scholar 

  12. National Institute for Allergy and Infectious Disease (NIAID), Division of AIDS. Table for grading the severity of adult and pediatric adverse events, version 2.0 (2014). Available at: http://rsc.tech-res.com/Document/safetyandpharmacovigilance/DAIDS_AE_Grading_Table_v2_NOV2014.pdf. Accessed 3 Dec 2015

  13. Pollack S, Weaver J (1993) Azidothymidine (AZT)-induced siderosis. Am J Hematol 43:230–233

    Article  CAS  PubMed  Google Scholar 

  14. 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–S30

    Article  Google Scholar 

  15. 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–e25

    Article  PubMed  PubMed Central  Google Scholar 

  16. 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 59:1332–1345

    Article  PubMed  Google Scholar 

  17. Vigilancia Epidemiológica del VIH/SIDA en España. Actualización 30 de Junio de 2014. Instituto de Salud Carlos III, Gobierno de España. Available at: http://www.msssi.gob.es/ciudadanos/enfLesiones/enfTransmisibles/sida/vigilancia/InformeVIHSida_Junio2014.pdf. Accessed 3 Dec 2015

Download references

Authors’ contribution

Núria Rovira, Antoni Noguera-Julian, Claudia Fortuny, and Rebeca Lahoz designed the study, collected and analyzed data, debated about conclusions, and wrote the paper. Susana Rives and Ruben Berrueco analyzed and discussed hematological data and reviewed the manuscript.

Author information

Authors and Affiliations

  1. Infectious Diseases Unit, Pediatrics Department, Hospital Sant Joan de Déu, Universitat de Barcelona, Passeig Sant Joan de Déu 2, 08950, Esplugues, Spain

    Núria Rovira, Antoni Noguera-Julian & Clàudia Fortuny

  2. Pediatric Hematology and Oncology Department, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain

    Susana Rives & Rubén Berrueco

  3. Pediatrics Department, Hospital Universitari Joan XXIII, Carrer Dr. Mallafrè Guasch 4, 43005, Tarragona, Spain

    Rebeca Lahoz

Authors
  1. Núria Rovira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antoni Noguera-Julian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Susana Rives
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rubén Berrueco
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rebeca Lahoz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Clàudia Fortuny
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Clàudia Fortuny.

Ethics declarations

Funding

This study was funded by Fundación para la Investigación y Prevención del SIDA en España, award number 240813/09.

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Communicated by David Nadal

Revisions received: 22 March 2016; 23 April 2016

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rovira, N., Noguera-Julian, A., Rives, S. et al. Influence of new antiretrovirals on hematological toxicity in HIV-exposed uninfected infants. Eur J Pediatr 175, 1013–1017 (2016). https://doi.org/10.1007/s00431-016-2730-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-016-2730-x

Keywords

Search

Navigation