Horizon 1 1 17 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES Aids 761-768 children dynamic model HIV population pharmacokinetics BURKINA FASO 2013 PAR00010316 ENG Aids 0269-9370 ISI:000315524700009 5 10.1097/QAD.0b013e32835caad1 https://www.documentation.ird.fr/hor/PAR00010316 https://www.documentation.ird.fr/intranet/publi/2024-12/010091860.pdf 27 Horizon (IRD) 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. 052 ; 050 ; 020 UR233