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Bouazza N., Treluyer J. M., Msellati Philippe, Van de Perre P., Diagbouga S., Nacro B., Hien H., Zoure E., Rouet F., Ouiminga A., Blanche S., Hirt D., Urien S. (2013). A novel pharmacokinetic approach to predict virologic failure in HIV-1-infected paediatric patients. Aids, 27 (5), 761-768. ISSN 0269-9370

Lien direct chez l'éditeur doi:10.1097/QAD.0b013e32835caad1

Titre
A novel pharmacokinetic approach to predict virologic failure in HIV-1-infected paediatric patients
Année de publication2013
Type de documentArticle référencé dans le Web of Science WOS:000315524700009
AuteursBouazza N., Treluyer J. M., Msellati Philippe, Van de Perre P., Diagbouga S., Nacro B., Hien H., Zoure E., Rouet F., Ouiminga A., Blanche S., Hirt D., Urien S.
SourceAids, 2013, 27 (5), p. 761-768. ISSN 0269-9370
RésuméObjective: 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.
Plan de classementEntomologie médicale / Parasitologie / Virologie [052] ; Santé : généralités [050] ; Sciences fondamentales / Techniques d'analyse et de recherche [020]
Descr. géo.BURKINA FASO
LocalisationFonds IRD
Identifiant IRDPAR00010316
Lien permanenthttp://www.documentation.ird.fr/hor/PAR00010316

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