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Severe efavirenz associated neurotoxicity: A retrospective cohort study

BACKGROUND: Efavirenz (EFV) is associated with neuropsychiatric symptoms. Severe neurotoxicity has been reported but the clinical phenotype and risk factors are poorly defined. OBJECTIVES: To characterise clinical presentations, risk factors and outcomes to help clinicians recognise severe neurotoxi...

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Autores principales: Arnab, Priyadarshini, Croxford, Roland, Scott, Janet, Perumal, Sameshan, Mohammed, Zahraa, Wiesner, Lubbe, Cohen, Karen, Wasserman, Sean
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AOSIS 2023
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10397354/
https://www.ncbi.nlm.nih.gov/pubmed/37780199
http://dx.doi.org/10.4102/sajid.v38i1.522
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author Arnab, Priyadarshini
Croxford, Roland
Scott, Janet
Perumal, Sameshan
Mohammed, Zahraa
Wiesner, Lubbe
Cohen, Karen
Wasserman, Sean
author_facet Arnab, Priyadarshini
Croxford, Roland
Scott, Janet
Perumal, Sameshan
Mohammed, Zahraa
Wiesner, Lubbe
Cohen, Karen
Wasserman, Sean
author_sort Arnab, Priyadarshini
collection PubMed
description BACKGROUND: Efavirenz (EFV) is associated with neuropsychiatric symptoms. Severe neurotoxicity has been reported but the clinical phenotype and risk factors are poorly defined. OBJECTIVES: To characterise clinical presentations, risk factors and outcomes to help clinicians recognise severe neurotoxicity earlier. METHOD: The authors retrospectively identified adults with supratherapeutic EFV concentrations (> 4 mg/L) obtained during routine clinical care in Cape Town, South Africa. Clinical and laboratory data at the time of EFV quantification were extracted from medical records. Logistic regression was performed to identify associations with neuropsychiatric symptoms, and with severe neurotoxicity. RESULTS: Eighty one patients were included; 62 with neuropsychiatric manifestations (most frequently ataxia [n = 20] and psychomotor slowing [n = 24]); and 19 with hepatotoxicity. Overall, 28 (34.6%) were male, 49 (60.5%) had concomitant isoniazid exposure, and median EFV concentration was 12.1 mg/L (interquartile range [IQR]: 6.6–20.0). Neuropsychiatric symptoms were associated with longer duration of EFV therapy, adjusted odds ratio (aOR) 1.3/180-day increment (95% confidence interval [CI]: 1.0–1.7); higher EFV concentrations, aOR 1.2/1 mg/L increase (95% CI: 1.0–1.4) and isoniazid exposure, aOR 8.2 (95% CI: 2.5–26.7). Severe neuropsychiatric symptoms occurred in 47 (75%) patients at a median of 5.9 months (IQR: 2.1–40.8) after EFV initiation. Severe symptoms odds were 1.2-fold higher (95% CI: 1.1–1.4) per 1 mg/L increase in EFV concentration. Symptoms resolved completely within 1 month in 25 (76%) patients with severe neurotoxicity who discontinued EFV. CONCLUSION: A concentration–effect relationship for severe neurotoxicity exists, which occurred late and resolved in most patients after EFV discontinuation. CONTRIBUTION: The authors highlighted clinical heterogeneity and morbidity of EFV-associated neurotoxicity.
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spelling pubmed-103973542023-09-26 Severe efavirenz associated neurotoxicity: A retrospective cohort study Arnab, Priyadarshini Croxford, Roland Scott, Janet Perumal, Sameshan Mohammed, Zahraa Wiesner, Lubbe Cohen, Karen Wasserman, Sean S Afr J Infect Dis Original Research BACKGROUND: Efavirenz (EFV) is associated with neuropsychiatric symptoms. Severe neurotoxicity has been reported but the clinical phenotype and risk factors are poorly defined. OBJECTIVES: To characterise clinical presentations, risk factors and outcomes to help clinicians recognise severe neurotoxicity earlier. METHOD: The authors retrospectively identified adults with supratherapeutic EFV concentrations (> 4 mg/L) obtained during routine clinical care in Cape Town, South Africa. Clinical and laboratory data at the time of EFV quantification were extracted from medical records. Logistic regression was performed to identify associations with neuropsychiatric symptoms, and with severe neurotoxicity. RESULTS: Eighty one patients were included; 62 with neuropsychiatric manifestations (most frequently ataxia [n = 20] and psychomotor slowing [n = 24]); and 19 with hepatotoxicity. Overall, 28 (34.6%) were male, 49 (60.5%) had concomitant isoniazid exposure, and median EFV concentration was 12.1 mg/L (interquartile range [IQR]: 6.6–20.0). Neuropsychiatric symptoms were associated with longer duration of EFV therapy, adjusted odds ratio (aOR) 1.3/180-day increment (95% confidence interval [CI]: 1.0–1.7); higher EFV concentrations, aOR 1.2/1 mg/L increase (95% CI: 1.0–1.4) and isoniazid exposure, aOR 8.2 (95% CI: 2.5–26.7). Severe neuropsychiatric symptoms occurred in 47 (75%) patients at a median of 5.9 months (IQR: 2.1–40.8) after EFV initiation. Severe symptoms odds were 1.2-fold higher (95% CI: 1.1–1.4) per 1 mg/L increase in EFV concentration. Symptoms resolved completely within 1 month in 25 (76%) patients with severe neurotoxicity who discontinued EFV. CONCLUSION: A concentration–effect relationship for severe neurotoxicity exists, which occurred late and resolved in most patients after EFV discontinuation. CONTRIBUTION: The authors highlighted clinical heterogeneity and morbidity of EFV-associated neurotoxicity. AOSIS 2023-07-24 /pmc/articles/PMC10397354/ /pubmed/37780199 http://dx.doi.org/10.4102/sajid.v38i1.522 Text en © 2023. The Authors https://creativecommons.org/licenses/by/4.0/Licensee: AOSIS. This work is licensed under the Creative Commons Attribution License.
spellingShingle Original Research
Arnab, Priyadarshini
Croxford, Roland
Scott, Janet
Perumal, Sameshan
Mohammed, Zahraa
Wiesner, Lubbe
Cohen, Karen
Wasserman, Sean
Severe efavirenz associated neurotoxicity: A retrospective cohort study
title Severe efavirenz associated neurotoxicity: A retrospective cohort study
title_full Severe efavirenz associated neurotoxicity: A retrospective cohort study
title_fullStr Severe efavirenz associated neurotoxicity: A retrospective cohort study
title_full_unstemmed Severe efavirenz associated neurotoxicity: A retrospective cohort study
title_short Severe efavirenz associated neurotoxicity: A retrospective cohort study
title_sort severe efavirenz associated neurotoxicity: a retrospective cohort study
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10397354/
https://www.ncbi.nlm.nih.gov/pubmed/37780199
http://dx.doi.org/10.4102/sajid.v38i1.522
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