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Title: Role of efavirenz plasma concentrations on long-term HIV suppression and immune restoration in HIV-infected children
Authors: Nontiya Homkham
Tim R. Cressey
Naim Bouazza
Lily Ingsrisawang
Pornchai Techakunakorn
Jutarat Mekmullica
Thitiporn Borkird
Achara Puangsombat
Sathaporn Na-Rajsima
Jean Marc Treluyer
Saik Urien
Gonzague Jourdain
Keywords: Agricultural and Biological Sciences
Biochemistry, Genetics and Molecular Biology
Issue Date: 1-May-2019
Abstract: © 2019 Homkham et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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 (C12). 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 log10 copies/mL (4.6 to 5.4), and CD4 cell count 71 cells/mm3. 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 C12 <1.0 mg/L. Conclusion The ISEFV score was a good predictor of viral replication in children on efavirenz-based treatment.
ISSN: 19326203
Appears in Collections:CMUL: Journal Articles

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