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. 2023 Jul 24;38(1):522.
doi: 10.4102/sajid.v38i1.522. eCollection 2023.

Severe efavirenz associated neurotoxicity: A retrospective cohort study

Priyadarshini Arnab  1 , Roland Croxford  2 , Janet Scott  2 , Sameshan Perumal  3 , Zahraa Mohammed  1 , Lubbe Wiesner  4 , Karen Cohen  5 , Sean Wasserman  1
Affiliations

Severe efavirenz associated neurotoxicity: A retrospective cohort study

Priyadarshini Arnab et al. S Afr J Infect Dis. .

Abstract

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.

Keywords: Cape Town; cerebellar; efavirenz; isoniazid; neurotoxicity; risk factors.

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Conflict of interest statement

The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article.

Figures

FIGURE 1
FIGURE 1
Empiric cumulative distribution function showing probability of efavirenz toxicity over time.
FIGURE 2
FIGURE 2
Kaplan–Meier plot comparing survival probability of neuropsychiatric and non-neuropsychiatric (hepatitis) symptoms.
FIGURE 1-A1
FIGURE 1-A1
Consort diagram showing selection of cases for study.
FIGURE 2-A1
FIGURE 2-A1
Box and whisker plot showing distribution of Efavirenz concentrations by gender.
See this image and copyright information in PMC

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