Homkham N., Cressey T. R., Bouazza N., Ingsrisawang L., Techakunakorn P., Mekmullica J., Borkird T., Puangsombat A., Na-Rajsima S., Treluyer J. M., Urien S., Jourdain Gonzague. (2019). Role of efavirenz plasma concentrations on long-term HIV suppression and immune restoration in HIV-infected children. PLoS One, 14 (5), p. e0216868 [12 p.]. ISSN 1932-6203.
Titre du document
Role of efavirenz plasma concentrations on long-term HIV suppression and immune restoration in HIV-infected children
Année de publication
2019
Auteurs
Homkham N., Cressey T. R., Bouazza N., Ingsrisawang L., Techakunakorn P., Mekmullica J., Borkird T., Puangsombat A., Na-Rajsima S., Treluyer J. M., Urien S., Jourdain Gonzague
Source
PLoS One, 2019,
14 (5), p. e0216868 [12 p.] ISSN 1932-6203
Background To access the long term relationship between efavirenz plasma concentrations and evolution of HIV RNA loads and CD4 cell counts in children. Methods Retrospective analysis of data from HIV-infected children on first line efavirenz-containing regimen. A population pharmacokinetic-pharmacodynamic (PK-PD) model was developed to describe the evolution of HIV RNA load and CD4 cell count (efficacy outcomes) in relation to efavirenz plasma concentration. Individual CYP2B6 516 G>T genotype data were not available for this analysis. A score (ISEFV) quantifying the effect of efavirenz concentrations on the long-term HIV replication was calculated from efavirenz concentrations and PD parameters and, a value of ISEFV below which HIV replication is likely not suppressed was determined. Cox proportional hazards regression models were used to assess the association of the risk of viral replication with ISEFV, and with efavirenz mid-dose concentration (C-12). Results At treatment initiation, median (interquartile range, IQR) age was 8 years (5 to 10), body weight 17 kg (14 to 23), HIV RNA load 5.1 log(10) copies/mL (4.6 to 5.4), and CD4 cell count 71 cells/mm(3). A model of PK-PD viral dynamics assuming that efavirenz decreases the rate of infected host cells adequately described the relationship of interest. After adjusting for age, baseline HIV RNA load and CD4 cell counts an ISEFV < 85% was significantly associated with a higher risk of viral replication (p-value < 0.001) while no significant association was observed with C-12 < 1.0 mg/L. Conclusion The ISEFV score was a good predictor of viral replication in children on efavirenz-based treatment.
Plan de classement
Santé : généralités [050]
;
Entomologie médicale / Parasitologie / Virologie [052]
Localisation
Fonds IRD [F B010075718]
Identifiant IRD
fdi:010075718
