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Case report: Severe central nervous system manifestations associated with aberrant efavirenz metabolism in children: the role of CYP2B6 genetic variation

BACKGROUND: Efavirenz, widely used as part of antiretroviral drug regimens in the treatment of paediatric human immunodeficiency virus infection, has central nervous system side effects. We describe four children presenting with serious, persistent central nervous system adverse events who were foun...

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Autores principales: Pinillos, Francoise, Dandara, Collet, Swart, Marelize, Strehlau, Renate, Kuhn, Louise, Patel, Faeezah, Coovadia, Ashraf, Abrams, Elaine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4735961/
https://www.ncbi.nlm.nih.gov/pubmed/26831894
http://dx.doi.org/10.1186/s12879-016-1381-x
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author Pinillos, Francoise
Dandara, Collet
Swart, Marelize
Strehlau, Renate
Kuhn, Louise
Patel, Faeezah
Coovadia, Ashraf
Abrams, Elaine
author_facet Pinillos, Francoise
Dandara, Collet
Swart, Marelize
Strehlau, Renate
Kuhn, Louise
Patel, Faeezah
Coovadia, Ashraf
Abrams, Elaine
author_sort Pinillos, Francoise
collection PubMed
description BACKGROUND: Efavirenz, widely used as part of antiretroviral drug regimens in the treatment of paediatric human immunodeficiency virus infection, has central nervous system side effects. We describe four children presenting with serious, persistent central nervous system adverse events who were found to have elevated plasma efavirenz concentrations as a result of carrying CYP2B6 single nucleotide polymorphisms, known to play a role in the metabolism of EFV. None of the children had a CYP2B6 wildtype haplotype. We believe this is the first case of cerebellar dysfunction associated with efavirenz use to be described in children. CASE PRESENTATION: Four black African children, between the ages of 4 and 8 years presenting between 1 and 20 months post-efavirenz initiation, are described. Cerebellar dysfunction, generalised seizures and absence seizures were the range of presenting abnormalities. Plasma efavirenz levels ranged from 20-60 mg/L, 5–15 times the upper limit of the suggested reference range. All abnormal central nervous system manifestations abated after efavirenz discontinuation. CONCLUSION: Efavirenz toxicity should always be considered in human immunodeficiency virus-infected children with unexplained central nervous system abnormalities. Our findings further our understanding of the impact of genetic variants on antiretroviral pharmacokinetics in children across various ethnic groups. Screening for potential EFV-toxicity based on the CYP2B6 c.516 SNP alone, may not be adequate.
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spelling pubmed-47359612016-02-03 Case report: Severe central nervous system manifestations associated with aberrant efavirenz metabolism in children: the role of CYP2B6 genetic variation Pinillos, Francoise Dandara, Collet Swart, Marelize Strehlau, Renate Kuhn, Louise Patel, Faeezah Coovadia, Ashraf Abrams, Elaine BMC Infect Dis Case Report BACKGROUND: Efavirenz, widely used as part of antiretroviral drug regimens in the treatment of paediatric human immunodeficiency virus infection, has central nervous system side effects. We describe four children presenting with serious, persistent central nervous system adverse events who were found to have elevated plasma efavirenz concentrations as a result of carrying CYP2B6 single nucleotide polymorphisms, known to play a role in the metabolism of EFV. None of the children had a CYP2B6 wildtype haplotype. We believe this is the first case of cerebellar dysfunction associated with efavirenz use to be described in children. CASE PRESENTATION: Four black African children, between the ages of 4 and 8 years presenting between 1 and 20 months post-efavirenz initiation, are described. Cerebellar dysfunction, generalised seizures and absence seizures were the range of presenting abnormalities. Plasma efavirenz levels ranged from 20-60 mg/L, 5–15 times the upper limit of the suggested reference range. All abnormal central nervous system manifestations abated after efavirenz discontinuation. CONCLUSION: Efavirenz toxicity should always be considered in human immunodeficiency virus-infected children with unexplained central nervous system abnormalities. Our findings further our understanding of the impact of genetic variants on antiretroviral pharmacokinetics in children across various ethnic groups. Screening for potential EFV-toxicity based on the CYP2B6 c.516 SNP alone, may not be adequate. BioMed Central 2016-02-02 /pmc/articles/PMC4735961/ /pubmed/26831894 http://dx.doi.org/10.1186/s12879-016-1381-x Text en © Pinillos et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Case Report
Pinillos, Francoise
Dandara, Collet
Swart, Marelize
Strehlau, Renate
Kuhn, Louise
Patel, Faeezah
Coovadia, Ashraf
Abrams, Elaine
Case report: Severe central nervous system manifestations associated with aberrant efavirenz metabolism in children: the role of CYP2B6 genetic variation
title Case report: Severe central nervous system manifestations associated with aberrant efavirenz metabolism in children: the role of CYP2B6 genetic variation
title_full Case report: Severe central nervous system manifestations associated with aberrant efavirenz metabolism in children: the role of CYP2B6 genetic variation
title_fullStr Case report: Severe central nervous system manifestations associated with aberrant efavirenz metabolism in children: the role of CYP2B6 genetic variation
title_full_unstemmed Case report: Severe central nervous system manifestations associated with aberrant efavirenz metabolism in children: the role of CYP2B6 genetic variation
title_short Case report: Severe central nervous system manifestations associated with aberrant efavirenz metabolism in children: the role of CYP2B6 genetic variation
title_sort case report: severe central nervous system manifestations associated with aberrant efavirenz metabolism in children: the role of cyp2b6 genetic variation
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4735961/
https://www.ncbi.nlm.nih.gov/pubmed/26831894
http://dx.doi.org/10.1186/s12879-016-1381-x
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