%0 Journal Article
%9 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES
%A Bouazza, N.
%A Treluyer, J. M.
%A Msellati, Philippe
%A Van de Perre, P.
%A Diagbouga, S.
%A Nacro, B.
%A Hien, H.
%A Zoure, E.
%A Rouet, F.
%A Ouiminga, A.
%A Blanche, S.
%A Hirt, D.
%A Urien, S.
%T A novel pharmacokinetic approach to predict virologic failure in HIV-1-infected paediatric patients
%D 2013
%L PAR00010316
%G ENG
%J Aids
%@ 0269-9370
%K children ; dynamic model ; HIV ; population pharmacokinetics
%K BURKINA FASO
%M ISI:000315524700009
%N 5
%P 761-768
%R 10.1097/QAD.0b013e32835caad1
%U https://www.documentation.ird.fr/hor/PAR00010316
%V 27
%W Horizon (IRD)
%X Objective: The objective of this study was to develop in children an HIV dynamic model able to predict simultaneously the viral load and CD4(+) lymphocyte evolutions, and to take into account, through a composite inhibition score, the relative contribution of each drug of the combination efavirenz-didanosine-lamivudine and use this score as a predictor of treatment failure in a multidrug therapy. Design: Open phase II trial (BURKINAME - ANRS 12103) registered in the ClinicalTrials. gov database (http://clinicaltrials.gov) with the no. NCT00122538. Methods: Forty-nine children aged from 2.5 to 15 years were administered once-daily dose of lamivudine, didanosine and efavirenz. The three drugs effect was then characterized by a composite inhibition score combining the effect of each drug, according to their site and mechanism of action and their relative contribution. Results: Efavirenz was the most potent antiretroviral and was responsible for 65% of the total effect, and then didanosine for 23% and lamivudine was the less potent with 12% of the total observed effect. An EC90 for efavirenz was determined (3.3 mg/l). AUC(90) was estimated for lamivudine and didanosine: 8.4 and 1.5mgh/l, respectively. The composite inhibition score was the best predictor of virologic failure compared with the concentrations of each drug taken independently [hazard ratio (HR) 0.6 per 10% increase, 95% confidence interval (CI) 0.41-0.88]. Conclusion: The relative contributions of three combined drugs were assessed on plasma viral load and CD4(+) lymphocyte count kinetics in HIV-1-infected children. Pharmacokinetics targets have been suggested for lamivudine and didanosine. A composite inhibition score has been determined to be a high predictor of treatment failure in a multidrug therapy.
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