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

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dc.contributor.authorAbrams, Elaine
dc.date.accessioned2021-10-08T06:20:26Z
dc.date.available2021-10-08T06:20:26Z
dc.date.issued2015
dc.description.abstractBackgroundEfavirenz, 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 presentationFour black African children, between the ages of 4 and 8years presenting between 1 and 20months post-efavirenz initiation, are described. Cerebellar dysfunction, generalised seizures and absence seizures were the range of presenting abnormalities. Plasma efavirenz levels ranged from 20-60mg/L, 5–15 times the upper limit of the suggested reference range. All abnormal central nervous system manifestations abated after efavirenz discontinuation.ConclusionEfavirenz 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.
dc.identifier.apacitationAbrams, E. (2015). Case report: Severe central nervous system manifestations associated with aberrant efavirenz metabolism in children: the role of CYP2B6 genetic variation. <i>BMC Infectious Diseases</i>, 16(1), 174 - 177. http://hdl.handle.net/11427/34277en_ZA
dc.identifier.chicagocitationAbrams, Elaine "Case report: Severe central nervous system manifestations associated with aberrant efavirenz metabolism in children: the role of CYP2B6 genetic variation." <i>BMC Infectious Diseases</i> 16, 1. (2015): 174 - 177. http://hdl.handle.net/11427/34277en_ZA
dc.identifier.citationAbrams, E. 2015. Case report: Severe central nervous system manifestations associated with aberrant efavirenz metabolism in children: the role of CYP2B6 genetic variation. <i>BMC Infectious Diseases.</i> 16(1):174 - 177. http://hdl.handle.net/11427/34277en_ZA
dc.identifier.issn1471-2334
dc.identifier.ris TY - Journal Article AU - Abrams, Elaine AB - BackgroundEfavirenz, 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 presentationFour black African children, between the ages of 4 and 8years presenting between 1 and 20months post-efavirenz initiation, are described. Cerebellar dysfunction, generalised seizures and absence seizures were the range of presenting abnormalities. Plasma efavirenz levels ranged from 20-60mg/L, 5–15 times the upper limit of the suggested reference range. All abnormal central nervous system manifestations abated after efavirenz discontinuation.ConclusionEfavirenz 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. DA - 2015 DB - OpenUCT DP - University of Cape Town IS - 1 J1 - BMC Infectious Diseases LK - https://open.uct.ac.za PY - 2015 SM - 1471-2334 T1 - Case report: Severe central nervous system manifestations associated with aberrant efavirenz metabolism in children: the role of CYP2B6 genetic variation TI - Case report: Severe central nervous system manifestations associated with aberrant efavirenz metabolism in children: the role of CYP2B6 genetic variation UR - http://hdl.handle.net/11427/34277 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/34277
dc.identifier.vancouvercitationAbrams E. Case report: Severe central nervous system manifestations associated with aberrant efavirenz metabolism in children: the role of CYP2B6 genetic variation. BMC Infectious Diseases. 2015;16(1):174 - 177. http://hdl.handle.net/11427/34277.en_ZA
dc.language.isoeng
dc.publisher.departmentDivision of Human Genetics
dc.publisher.facultyFaculty of Health Sciences
dc.sourceBMC Infectious Diseases
dc.source.journalissue1
dc.source.journalvolume16
dc.source.pagination174 - 177
dc.source.urihttps://dx.doi.org/10.1186/s12879-016-1381-x
dc.subject.otherCYP2B6
dc.subject.otherEpilepsy, Absence
dc.subject.otherCentral Nervous System Infections
dc.subject.otherCerebellar Diseases
dc.subject.otherSeizures
dc.subject.otherNervous System Malformations
dc.subject.otherPlasma
dc.subject.otherCentral Nervous System
dc.subject.otherCytochrome P-450 CYP2B6
dc.subject.otherGenetic Variation
dc.subject.otherPolymorphism, Single Nucleotide
dc.subject.otherHaplotypes
dc.subject.otherPharmacokinetics
dc.subject.otherMetabolism
dc.subject.otherTherapeutics
dc.subject.otherReference Values
dc.subject.otherHuman immunodeficiency virus 1
dc.subject.otherHomo sapiens
dc.subject.otherInfectious Diseases
dc.subject.otherParasitology
dc.subject.otherMedical Microbiology
dc.subject.otherTropical Medicine
dc.subject.otherInternal Medicine
dc.titleCase report: Severe central nervous system manifestations associated with aberrant efavirenz metabolism in children: the role of CYP2B6 genetic variation
dc.typeJournal Article
uct.type.publicationResearch
uct.type.resourceJournal Article
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