Severe efavirenz associated neurotoxicity: A retrospective cohort study

Southern African Journal of Infectious Diseases

 
 
Field Value
 
Title Severe efavirenz associated neurotoxicity: A retrospective cohort study
 
Creator Arnab, Priyadarshini Croxford, Roland Scott, Janet Peruma, Sameshan Mohammed, Zahraa Wiesner, Lubbe Cohen, Karen Wasserman, Sean
 
Subject Medicine; HIV efavirenz; isoniazid; risk factors; neurotoxicity; cerebellar; Cape Town
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.
 
Publisher AOSIS Publishing
 
Contributor Wellcome Trust, Wellcome Centre for Infectious Diseases Research in Africa
Date 2023-07-24
 
Type info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion — Retrospective; cohort study
Format text/html application/epub+zip text/xml application/pdf
Identifier 10.4102/sajid.v38i1.522
 
Source Southern African Journal of Infectious Diseases; Vol 38, No 1 (2023); 8 pages 2313-1810 2312-0053
 
Language eng
 
Relation
The following web links (URLs) may trigger a file download or direct you to an alternative webpage to gain access to a publication file format of the published article:

https://sajid.co.za/index.php/sajid/article/view/522/1242 https://sajid.co.za/index.php/sajid/article/view/522/1243 https://sajid.co.za/index.php/sajid/article/view/522/1244 https://sajid.co.za/index.php/sajid/article/view/522/1245
 
Coverage South Africa; Cape Town Retrospective Adults; HIV positive; on ART
Rights Copyright (c) 2023 Priyadarshini Arnab, Roland Croxford, Janet Scott, Sameshan Perumal, Zahraa Mohammed, Lubbe Wiesner, Karen Cohen, Sean Wasserman https://creativecommons.org/licenses/by/4.0
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