@article{PAR00010316,
  title = {{A} novel pharmacokinetic approach to predict virologic failure in {HIV}-1-infected paediatric patients},
  author = {{B}ouazza, {N}. and {T}reluyer, {J}. {M}. and {M}sellati, {P}hilippe and {V}an de {P}erre, {P}. and {D}iagbouga, {S}. and {N}acro, {B}. and {H}ien, {H}. and {Z}oure, {E}. and {R}ouet, {F}. and {O}uiminga, {A}. and {B}lanche, {S}. and {H}irt, {D}. and {U}rien, {S}.},
  editor = {},
  language = {{ENG}},
  abstract = {{O}bjective: {T}he objective of this study was to develop in children an {HIV} dynamic model able to predict simultaneously the viral load and {CD}4(+) 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. {D}esign: {O}pen phase {II} trial ({BURKINAME} - {ANRS} 12103) registered in the {C}linical{T}rials. gov database (http://clinicaltrials.gov) with the no. {NCT}00122538. {M}ethods: {F}orty-nine children aged from 2.5 to 15 years were administered once-daily dose of lamivudine, didanosine and efavirenz. {T}he 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. {R}esults: {E}favirenz 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. {A}n {EC}90 for efavirenz was determined (3.3 mg/l). {AUC}(90) was estimated for lamivudine and didanosine: 8.4 and 1.5mgh/l, respectively. {T}he 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]. {C}onclusion: {T}he relative contributions of three combined drugs were assessed on plasma viral load and {CD}4(+) lymphocyte count kinetics in {HIV}-1-infected children. {P}harmacokinetics 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.},
  keywords = {children ; dynamic model ; {HIV} ; population pharmacokinetics ; {BURKINA} {FASO}},
  booktitle = {},
  journal = {{A}ids},
  volume = {27},
  numero = {5},
  pages = {761--768},
  ISSN = {0269-9370},
  year = {2013},
  DOI = {10.1097/{QAD}.0b013e32835caad1},
  URL = {https://www.documentation.ird.fr/hor/{PAR}00010316},
}