Case report: Severe central nervous system manifestations associated with aberrant efavirenz metabolism in children: the role of CYP2B6 genetic variation. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Pinillos, Francoise; Dandara, Collet; Swart, Marelize; Strehlau, Renate; Kuhn, Louise; Patel, Faeezah; Coovadia, Ashraf; Abrams, Elaine
• Is Part Of: BMC infectious diseases. Volume 16:Issue 1(2016)
• Page Start: 1
• Page End: 7
• Publication Date: 2015-12
• Subjects: Efavirenz -- Paediatrics -- CYP2B6 -- HIV -- Paediatric HIV -- Antiretroviral treatment -- CNS -- Seizures -- Cerebellum; Communicable diseases -- Periodicals; Sexually Transmitted Diseases -- Periodicals; 616.905
• DOI: 10.1186/s12879-016-1381-x
• Languages: English
• ISSNs: 1471-2334

Abstract

Abstract 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 carryingCYP2B6 single nucleotide polymorphisms, known to play a role in the metabolism of EFV. None of the children had aCYP2B6 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 theCYP2B6 c.516 SNP alone, may not be adequate.