Bouazza N. auteur aut IRD Tréluyer J. M. auteur aut IRD Msellati Philippe auteur aut IRD Van de Perre P. auteur aut IRD Diagbouga S. auteur aut IRD Nacro B. auteur aut IRD Hien H. auteur aut IRD Zoure E. auteur aut IRD Rouet F. auteur aut IRD Ouiminga A. auteur aut IRD Blanche S. auteur aut IRD Hirt D. auteur aut IRD Urien S. auteur aut IRD text journalArticle eng text/pdf born digital access 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. specialized children dynamic model HIV population pharmacokinetics BURKINA FASO 052 050 020 27 5 761-768 2013 0269-9370 https://www.documentation.ird.fr/hor/PAR00010316 10.1097/QAD.0b013e32835caad1 0269-9370 [F B010091860] https://www.documentation.ird.fr/hor/PAR00010316 https://www.documentation.ird.fr/intranet/publi/2024-12/010091860.pdf Accès réservé (Intranet de l'IRD) IRD - Base Horizon / Pleins textes 2013-05-02 2024-12-11 PAR00010316 fre