Potential implications of CYP3A4, CYP3A5 and MDR‐1 genetic variants on the efficacy of Lopinavir/Ritonavir (LPV/r) monotherapy in HIV‐1 patients

Introduction Several genetic single nucleotide polymorphisms (SNPs) in biotransformation enzymes (CYP3A4, CYP3A5) or transporter proteins (multidrug resistance MDR1 gene product, P‐gp) are involved in PI metabolism so that PI pharmacokinetics is characterized by a large inter‐individual variability....

Full description

Saved in:
Bibliographic Details
Published in:Journal of the International AIDS Society 2014-11, Vol.17 (4 Suppl 3), p.19589-n/a
Main Authors: Berno, Giulia, Zaccarelli, Mauro, Gori, Caterina, Tempestilli, Massimo, Pucci, Luigia, Antinori, Andrea, Perno, Carlo Federico, Paolo Pucillo, Leopoldo, D'Arrigo, Roberta
Format: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
AIDS
Antiretroviral drugs
Biotransformation
Dosage and administration
Drug therapy
Genetic factors
Genetic variance
Genetic variation
Health aspects
HIV
HIV patients
Human immunodeficiency virus
Lopinavir
Patients
Pharmacokinetics
Ritonavir
Testing
Therapeutic drug monitoring
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Introduction Several genetic single nucleotide polymorphisms (SNPs) in biotransformation enzymes (CYP3A4, CYP3A5) or transporter proteins (multidrug resistance MDR1 gene product, P‐gp) are involved in PI metabolism so that PI pharmacokinetics is characterized by a large inter‐individual variability. The aim of this study was: (i) to develop an in‐house PCR/direct sequencing, based on DNA purification of full‐length CYP3A4 and CYP3A5 genes (SNPs) and MDR1 C3435T variant; (ii) to investigate association of CYP3A4 and CYP3A5 reported or unreported genetic polymorphisms and MDR1‐C3435T (CC homozygote, CT heterozygote, TT homozygote) with clinical outcome of HIV‐1 infected subjects treated with PI. Methods Overall, 39 HIV‐1 infected patients receiving boosted Lopinavir (LPV/r) monotherapy after virological suppression were genotyped and analyzed through PCR and direct sequencing of full‐length CYP3A4 and CYP3A5 gene sequences [1] and MDR1 gene (C3435T). CD4+T‐cell counts and plasma viral load were analyzed before and after LPV/r initiation; LPV/r therapeutic drug monitoring (TDM) was determined at 12‐hours. Results LPV/r TDM (ng/ml) did not show significant differences among CYP3A4 or CYP3A5 SNPs, although a mean lower level of LPV/r was associated with detection of several SNPs: CYP3A5*3 rs776746; CYP3A5 rs28365088, CYP3A5 rs15524, CYP3A4 rs2687116, and a not already described polymorphism CYP3A4 nt20338. In follow‐up analysis,
ISSN:1758-2652
1758-2652
DOI:10.7448/IAS.17.4.19589