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A proposed management algorithm for late-onset efavirenz neurotoxicity

H M Cross, S Chetty, M T Asukile, H S Hussey, E B Lee Pan, L M Tucker

Abstract


A high proportion of HIV-positive patients in South Africa receive concomitant efavirenz (EFV) and isoniazid (INH) therapy. EFV is metabolised in the liver via CYP2B6, and genetic polymorphism of CYP2B6 is known to result in slowed metabolism of the drug. INH is also metabolised in the liver, causing inhibition of a pathway that plays an important role in slow EFV metabolisers. Concomitant INH use therefore affects plasma levels of EFV. EFV is well known to cause neuropsychiatric side-effects on initiation, and a recent adult case series described late-onset neurotoxicity in the form of subacute ataxia and encephalopathy in patients treated with EFV for a median of 2 years, in association with toxic plasma levels of the drug. We have seen an increase in cases of EFV toxicity presenting to our neurology referral unit. All cases have been in the context of recent initiation of concomitant INH. We therefore conducted a retrospective case record audit to describe these seven cases with the additional advantage of tertiary-level assessment. We outline the clinical features and investigation results, as well as outcomes after EFV was stopped. Our main objectives are to highlight the probable role of concomitant INH use in the development of this syndrome, and to suggest that only limited work-up may be warranted in suspected cases.


Authors' affiliations

H M Cross, Division of Neurology, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, South Africa

S Chetty, Division of Neurology, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, South Africa

M T Asukile, Division of Neurology, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, South Africa

H S Hussey, Division of Neurology, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, South Africa

E B Lee Pan, Division of Neurology, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, South Africa

L M Tucker, Division of Neurology, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, South Africa

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Keywords

HIV; Efavirenz; Neurotoxicity

Cite this article

South African Medical Journal 2018;108(4):271-274. DOI:10.7196/SAMJ.2018.v108i4.12914

Article History

Date submitted: 2018-03-28
Date published: 2018-03-28

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