Isoniazid and low body weight are important contributors to LENS development.Ītaxia efavirenz encephalopathy neurotoxicity pharmacogenetics. Our cohort provides definitive evidence that LENS is associated with the CYP2B6 slow metabolizer genotype, with a median efavirenz plasma concentration >12-fold higher than the defined upper limit of the therapeutic range. Efavirenz plasma concentration was markedly increased at 50.5 (47.0-65.4) µg/mL 8-hydroxyefavirenz concentration was markedly decreased at 0.10 (0.07-0.15) µg/mL. Thirteen were receiving the CYP2A6 enzyme inhibitor isoniazid, and all 15 were genotypic NAT2 slow or intermediate acetylators.
#Nightingale syndrome series#
In Doctor Who, Martha having to perform CPR on the Doctor might have helped develop her crush for him in series 3. Arguably Chuck and Eva on Gossip Girl, depending on whether or not you believe he had genuine feelings for her. All 15 participants were successfully genotyped as slow CYP2B6 metabolizers, with 6 participants additionally having CYP2A6 heterozygous genotype. George mistakenly calls it the 'Clara Nightingale Syndrome,' confusing Florence Nightingale with Clara Barton. Median weight was 49.9kg with a median duration on efavirenz of 2.2 years. Every purchase you make puts money in an artist’s pocket. Find Nightingale-inspired gifts and merchandise printed on quality products one at a time in socially responsible ways. Thirteen (13/15) were Black-African and 13 were female. T-shirts, stickers, wall art, home decor, and more designed and sold by independent artists. Median (IQR) plasma efavirenz and 8-hydroxyefavirenz were described.įifteen participants were enrolled. Pharmacokinetic analyses were performed using liquid chromatography-tandem mass spectrometry. Genetic polymorphisms known to be associated with increased efavirenz plasma concentrations in CYP2B6 (rs3745274, rs28399499, rs4803419) and CYP2A6 (rs28399433) were selected and used to determine proportions of slow metabolizers. The aim of our study was to determine the frequency of CYP2B6 slow metabolizers in participants with LENS.Īdult HIV-positive participants on efavirenz-based antiretroviral therapy presenting with LENS were prospectively enrolled.
We hypothesized that participants with LENS would predominantly be CYP2B6 slow metabolizers. Efavirenz is primarily metabolized by cytochrome P450 2B6 (CYP2B6), with CYP2A6 as an accessory pathway. The late-onset efavirenz neurotoxicity syndrome (LENS) presents as ataxia and/or encephalopathy with supratherapeutic efavirenz plasma concentrations (>4 µg/mL).
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