Imperial College London
Alternate

Emeritus ProfessorMyraMcClure

Faculty of Medicine, Department of Infectious Disease

Emeritus Professor of Retrovirology
 
 
 
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Contact

 

+44 (0)20 7594 3902m.mcclure

 
 
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Location

 

456Medical SchoolSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lamorde:2018:cid/ciy161,
author = {Lamorde, M and Wang, X and Neary, M and Bisdomini, E and Nakalema, S and Byakika-Kibwika, P and Mukonzo, JK and Khan, W and Owen, A and McClure, M and Boffito, M},
doi = {cid/ciy161},
journal = {Clinical Infectious Diseases},
pages = {785--790},
title = {Pharmacokinetics, pharmacodynamics, and pharmacogenetics of Efavirenz 400 mg once daily during pregnancy and post-partum},
url = {http://dx.doi.org/10.1093/cid/ciy161},
volume = {67},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundA clinical trial showed that efavirenz 400 mg once daily (EFV400) is as effective as the standard adult dose. World Health Organization recommends EFV400 as an alternative first-line agent, but data are lacking in the third trimester of pregnancy (TT). We investigated the pharmacokinetics, efficacy, and CYP2B6 pharmacogenetics in HIV-infected women (WLWH) on EFV400 during TT and post-partum (PP).MethodsAn open-label 2-center study (United Kingdom, Uganda) was conducted in WLWH receiving antiretroviral regimens containing efavirenz 600 mg, who had their efavirenz dose reduced to EFV400. Weekly therapeutic drug monitoring (TDM), steady-state pharmacokinetic profiles (TT and PP), safety, virological efficacy, and CYP2B6 polymorphisms at positions 516 (C > T) and 938 (T > C) were evaluated.ResultsTwenty-five WLWH of African origin were enrolled. All had viral loads <50 copies/mL at baseline, which were maintained throughout the study. No infant was HIV infected. No WLWH were withdrawn due to low EFV400 TDM results. Geometric mean ratios (TT/PP; 90% confidence interval) for EFV400 maximum observed plasma concentration, area under the curve, and plasma concentration measured 24 hours after the observed dose were 0.97 (.85–1.10), 0.87 (.76–.99), and 0.77 (.65–.91), respectively. Five of 25 WLWH were slow metabolizers.ConclusionsAlthough EFV400 pharmacokinetic parameters were slightly lower for TT compared with PP values, efavirenz concentrations exceeded cutoff levels established by the study and those measured in antiretroviral-naive patients receiving EFV400 in ENCORE1. All subjects maintained a viral load <50 copies/mL, suggesting that EFV400 can be used in pregnant WLWH.
AU  - Lamorde,M
AU  - Wang,X
AU  - Neary,M
AU  - Bisdomini,E
AU  - Nakalema,S
AU  - Byakika-Kibwika,P
AU  - Mukonzo,JK
AU  - Khan,W
AU  - Owen,A
AU  - McClure,M
AU  - Boffito,M
DO  - cid/ciy161
EP  - 790
PY  - 2018///
SN  - 1058-4838
SP  - 785
TI  - Pharmacokinetics, pharmacodynamics, and pharmacogenetics of Efavirenz 400 mg once daily during pregnancy and post-partum
T2  - Clinical Infectious Diseases
UR  - http://dx.doi.org/10.1093/cid/ciy161
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000442284400018&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/63109
VL  - 67
ER  -
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