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Neuropsychiatric complications of efavirenz in children with HIV-1 infection

Background: Efavirenz is associated with transient neuropsychiatric manifestations but the impact on neurocognition is unknown. Genetically determined black South Africans who are slow metabolizers of efavirenz may be at risk of toxicity. This study describes neuropsychiatric and neurocognitive mani...

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Main Author: Hammond Charles
Other Authors: Eley Brian
Format: Thesis
Language:English
Published: Division of Neurology 2019
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access_status_str Open Access
author Hammond Charles
author2 Eley Brian
author_browse Eley Brian
Hammond Charles
author_facet Eley Brian
Hammond Charles
author_sort Hammond Charles
collection Thesis
description Background: Efavirenz is associated with transient neuropsychiatric manifestations but the impact on neurocognition is unknown. Genetically determined black South Africans who are slow metabolizers of efavirenz may be at risk of toxicity. This study describes neuropsychiatric and neurocognitive manifestations of South African children with suspected efavirenz neurotoxicity. Method: This retrospective study describes clinical features of 12 children with suspected efavirenz neurotoxicity (2008 – 2014). Results: Twelve children were referred (aged 3 years 4 months to 12 years, mean 7 years 8 months; 8 indigenous African (black) and 4 mixed ancestry). Six had acute neuropsychiatric manifestations after 2-8 weeks (mean 5 weeks) on efavirenz including drowsiness, seizures, sleep disturbances, behavioural changes, ataxia and slurred speech. Symptoms resolved over a few weeks in four. Two black children were phenotypically slow metabolizers with high plasma efavirenz concentrations above normal range resulting in discontinuation of efavirenz. Nine children had neurocognitive concerns potentially exacerbated by long-term efavirenz (6-72 months therapy; mean 31 months), and showed poor performance in all neurocognitive domains. Conclusion: Efavirenz causes transient neuropsychiatric adverse effects and may contribute to poor longterm neurocognitive outcomes in HIV-infected children. Genetically slow metabolizers are at risk of neurotoxicity. Prospective studies comparing efavirenz-treated and efavirenz-naïve children are needed.
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institution University of Cape Town (South Africa)
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license_str Not specified — see source repository
provenance_str_mv Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository
publishDate 2019
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spelling oai:open.uct.ac.za:11427/29289 Neuropsychiatric complications of efavirenz in children with HIV-1 infection Hammond Charles Eley Brian Efavirenz neuropsychiatric neurocognitive children South Africa Background: Efavirenz is associated with transient neuropsychiatric manifestations but the impact on neurocognition is unknown. Genetically determined black South Africans who are slow metabolizers of efavirenz may be at risk of toxicity. This study describes neuropsychiatric and neurocognitive manifestations of South African children with suspected efavirenz neurotoxicity. Method: This retrospective study describes clinical features of 12 children with suspected efavirenz neurotoxicity (2008 – 2014). Results: Twelve children were referred (aged 3 years 4 months to 12 years, mean 7 years 8 months; 8 indigenous African (black) and 4 mixed ancestry). Six had acute neuropsychiatric manifestations after 2-8 weeks (mean 5 weeks) on efavirenz including drowsiness, seizures, sleep disturbances, behavioural changes, ataxia and slurred speech. Symptoms resolved over a few weeks in four. Two black children were phenotypically slow metabolizers with high plasma efavirenz concentrations above normal range resulting in discontinuation of efavirenz. Nine children had neurocognitive concerns potentially exacerbated by long-term efavirenz (6-72 months therapy; mean 31 months), and showed poor performance in all neurocognitive domains. Conclusion: Efavirenz causes transient neuropsychiatric adverse effects and may contribute to poor longterm neurocognitive outcomes in HIV-infected children. Genetically slow metabolizers are at risk of neurotoxicity. Prospective studies comparing efavirenz-treated and efavirenz-naïve children are needed. 2019-02-05T06:53:39Z 2019-02-05T06:53:39Z 2018 2019-01-31T11:11:46Z Master Thesis Masters MPhil http://hdl.handle.net/11427/29289 eng application/pdf Division of Neurology Faculty of Health Sciences University of Cape Town
spellingShingle Efavirenz
neuropsychiatric
neurocognitive
children
South Africa
Hammond Charles
Neuropsychiatric complications of efavirenz in children with HIV-1 infection
thesis_degree_str Master's
title Neuropsychiatric complications of efavirenz in children with HIV-1 infection
title_full Neuropsychiatric complications of efavirenz in children with HIV-1 infection
title_fullStr Neuropsychiatric complications of efavirenz in children with HIV-1 infection
title_full_unstemmed Neuropsychiatric complications of efavirenz in children with HIV-1 infection
title_short Neuropsychiatric complications of efavirenz in children with HIV-1 infection
title_sort neuropsychiatric complications of efavirenz in children with hiv 1 infection
topic Efavirenz
neuropsychiatric
neurocognitive
children
South Africa
url http://hdl.handle.net/11427/29289
work_keys_str_mv AT hammondcharles neuropsychiatriccomplicationsofefavirenzinchildrenwithhiv1infection