Efavirenz as a cause of ataxia in children

Hauptfleisch, Marc Peter Kedzlie; Moore, David P.; Rodda, J.

doi:10.7196/samj.2015.v105i11.9451

Cited by 12 publications

(7 citation statements)

References 11 publications

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“…It improved gradually with corresponding decline in the plasma EFV levels after treatment discontinuation. Ataxia has been reported in other South African children with supra-therapeutic efavirenz levels (16).…”

Section: Discussionmentioning

confidence: 87%

Neuropsychiatric and Neurocognitive Manifestations in HIV-Infected Children Treated With Efavirenz in South Africa—A Retrospective Case Series

et al. 2019

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Background: Efavirenz is associated with transient neuropsychiatric manifestations but the impact on neurocognition in children is unknown. Genetically 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 features consistent with efavirenz neurotoxicity between 2008 and 2014. Results: Twelve children (4 males, 8 females) aged 3–12 years (median 8.4 years) were referred to a dedicated pediatric neuroHIV service. Eight were of indigenous African (black) ancestry and 4 were of mixed ancestry. The total duration on efavirenz-containing ART at the time of referral was 6–72 (mean 31) months. Two children (both of black ancestry) were phenotypically slow metabolizers and presented with acute manifestations and high plasma efavirenz concentrations above normal range resulting in discontinuation of efavirenz. Ten other children had clinical presentations compatible with efavirenz neurotoxicity but had normal or sub-therapeutic plasma efavirenz concentrations and continued treatment with efavirenz. The acute neuropsychiatric manifestations reported included drowsiness, seizures, sleep disturbances, personality changes, ataxia, and slurred speech. These were noticed 2–8 weeks (mean 5 weeks) after commencing efavirenz and resolved over a few weeks. Nine children had neurocognitive deficits and showed poor performance in all neurocognitive domains that were tested. Interpretation: Efavirenz causes transient neuropsychiatric adverse effects and may contribute to poor long-term neurocognitive outcomes in HIV-infected children. Prospective studies comparing efavirenz-treated and efavirenz-naïve children are needed to further elucidate the manifestations of efavirenz toxicity.

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Section: Discussionmentioning

confidence: 87%

Neuropsychiatric and Neurocognitive Manifestations in HIV-Infected Children Treated With Efavirenz in South Africa—A Retrospective Case Series

et al. 2019

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“…Previous cohort studies have only included women, did not separate severe from milder symptoms and only small case series have documented severe EFV neuropsychiatric sequelae. 10,11,13,14 High rates of HIV-associated TB place patients in South Africa at particular risk of EFV neurotoxicity, especially given the relatively high background prevalence of 'slow metaboliser' genotypes and ongoing use of EFV for ART by some clinicians despite dolutegravir availability. However, the diagnosis may be missed because of overlap with other common neurological syndromes, and pharmacogenetic risk stratification may not be feasible in resource-limited settings.…”

Section: Introductionmentioning

confidence: 99%

Severe efavirenz associated neurotoxicity: A retrospective cohort study

Arnab,

Croxford,

Scott

et al. 2023

Southern African Journal of Infectious Diseases

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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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“…In another case report from South Africa efavirenz induced ataxia was identified in two girls, 6 and 13 year old who had received the offending drug for 1 and 1.5 years, respectively. [ 6 ] Hammond CK et al . in an analysis of 12 HIV children with neurocognitive manifestations while on efavirenz treatment have identified delayed toxicity in two patients [ Table 1 ].…”

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confidence: 99%