Evidence map›Paper›PMID 26831894›Full record

ArticleBMC infectious diseases2016

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

Francoise Pinillos, Collet Dandara, Marelize Swart, Renate Strehlau, Louise Kuhn, Faeezah Patel, Ashraf Coovadia, Elaine Abrams

Open access · goldAbstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC infectious diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.

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  11. PromotingInternational journal of environmental research and public health · 2020
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  18. Reply to Van de Wijer et al.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 3 countries.

Francoise PinillosEmpilweni Services and Research Unit (ESRU), Rahima Moosa Mother and Child Hospital, Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Collet DandaraPharmacogenetics and Cancer Research Group, Division of Human Genetics, Department of Pathology & Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Marelize SwartPharmacogenetics and Cancer Research Group, Division of Human Genetics, Department of Pathology & Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Renate StrehlauEmpilweni Services and Research Unit (ESRU), Rahima Moosa Mother and Child Hospital, Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Louise KuhnGertrude H. Sergievsky Center, College of Physicians and Surgeons; and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
Faeezah PatelEmpilweni Services and Research Unit (ESRU), Rahima Moosa Mother and Child Hospital, Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Ashraf CoovadiaEmpilweni Services and Research Unit (ESRU), Rahima Moosa Mother and Child Hospital, Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Elaine AbramsICAP, Mailman School of Public Health, and College of Physicians & Surgeons Columbia University, 722 W168th street, New York, NY, 10032, USA. eja1@columbia.edu.
Western Cape Department of Health · ZAUniversity of Cape Town · ZAColumbia University · USRoyal College of Physicians · GB

Funding

Treatment Options for Protease Inhibitor Exposed ChildrenR01HD061255 · NICHD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI KUHN, LOUISE · 2010 to 2014
$2.9M
NICHD NIH HHS R01 HD061255
6 · The paper itself

Abstract

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 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.

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.

Indexed as

Polymorphism, Single NucleotideAlkynesAnti-HIV AgentsBenzoxazinesCentral Nervous SystemChildChild, PreschoolCyclopropanesCytochrome P-450 CYP2B6FemaleHaplotypesHIV InfectionsHumansMaleAlkynesAnti-HIV AgentsBenzoxazinesCyclopropanesCYP2B6 protein, humanCytochrome P-450 CYP2B6efavirenz

Identifiers

PMID26831894
PMCPMC4735961
OpenAlexW2253998502

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.