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Updated: Feb 10, 2026

Genotypic Inference of HIV-1 Tropism Using Population-based Sequencing of V3
Published on: December 27, 2010
Population pharmacokinetic/pharmacogenetic model of lopinavir/ritonavir in HIV-infected patients
Elena López Aspiroz1, Dolores Santos Buelga2, Salvador Enrique Cabrera Figueroa1,3
1Pharmacy Service, University Hospital of Salamanca, Paseo de San Vicente 58, 37007 Salamanca, Spain.
Aim:
This study aims to develop a population pharmacokinetic/pharmacogenetic model for lopinavir/ritonavir (LPV/r) in European HIV-infected patients.
Materials & Methods:
A total of 693 LPV/r plasma concentrations were assessed and 15 single-nucleotide polymorphisms were genotyped. The population pharmacokinetic/pharmacogenetic model was created using a nonlinear mixed-effect approach (NONMEM® v.7.2.0., ICON Development Solutions, Dublin, Ireland).
Results:
Covariates significantly related to LPV/r apparent clearance (CL/F) were ritonavir trough concentration (RTC), BMI, high-density lipoprotein cholesterol (HDL-C) and certain single-nucleotide polymorphisms in genes encoding for metabolizing enzymes, which are representable as follows: CL/F = (0.216BMI + 0.0125HDL-C) × 0.713RTC × 1.26rs28371764[C/T] × 0.528rs6945984[C/C] × 0.302 CYP3A4[1461insA/del] Conclusion: The LPV/r standard dose appears to be appropriate for the rs28371764[C/T] genotype. However, lower doses should be recommended for the rs6945984[C/C] and CYP3A4[1461insA/del] genotypes and even for those patients without any of these variants, as the standard dose seems to be higher than that which is required in order to achieve therapeutic levels.
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