1. Stampa a cura della S.S. Relazioni Esterne
ASL CITTA’ di TORINO
PHARMACOGENETICS PREDICTION OF LIPID TOXICITY IN HIV-PATIENTS TREATED WITH EFAVIRENZ.
Sarah Allegra, Jessica Cusato, Andrea Calcagno, Letizia Marinaro, Stefano Bonora, Giovanni Di Perri,
Antonio D'Avolio.
Department of Medical Sciences, University of Turin, ASL "Città di Torino“, Laboratory of Clinical Pharmacology and Pharmacogenetics of Medical Sciences (UNI EN ISO 9001:2008 and 13485:2016 (CE-IVD) certified laboratory), Amedeo di Savoia Hospital, Turin (TO), Italy
INTRODUCTION
Efavirenz is a non-nucleoside reverse transcriptase inhibitor, related to increased high-density (HDL) and low-density lipoprotein (LDL) and total cholesterol (COLt) concentrations in adults and children.
Higher drug plasma concentrations have been associated with raised plasma lipid and glucose concentrations.
Single-nucleotide polymorphism CYP2B6 516 G>T is known to be associated with higher drug plasma concentrations (1). Moreover, CYP2B6 516 TT genotype showed increased HDL levels, compared to GG/GT group, after 48 weeks of treatment (2).
These observations highlight the possible influence of pharmacogenetic in changing cholesterol concentrations in patients on efavirenz treatment.
We investigated whether single nucleotide polymorphisms (SNPs) could predict variations in plasma lipid (HDL, LDL, and COLt) at different timings (12/24/48 weeks of therapy), in patients treated with efavirenz.
RESULTS
Forty-eight patients (37 males, 43 Caucasians, median age 41 years) were included.
CAR 540 TT genotype resulted able to predict reduced values of:
Δ12 COLt (p=0.001);
HDL (p=0.002);
LDL (p=0.001);
Δ24 HDL (p=0.016).
VEGFA AC/CC genotype group remained as positive predictor of:
Δ12 COLt (p=0.021);
HDL (p=0.008).
VEGFA -614 AG/GG genotype resulted as negative predictor of:
Δ12 HDL (p=0.012).
BCRP CC genotype remained as positive predictor of:
COLt Δ12 (p=0.034);
COLt Δ24 (p=0.008).
BCRP TC/CC AG/GG genotype resulted as negative predictor of:
Δ24 HDL (p=0.020);
Δ24 LDL (p=0.031);
Δ48 LDL p=0.029).
BSEP CC genotype remained as positive predictor of:
Δ24 COLt (p=0.032).
MATERIALS AND METHODS
Adult HIV-positive patients treated with efavirenz were enrolled. For HDL, LDL, COLt and GLUC levels, a delta (Δ) value was calculated for each interval from baseline: 12/24/48 weeks minus baseline, called Δ12, Δ24 and Δ48, respectively.
Allelic discrimination of MDR1 3435C>T, 1236C>T, 2677G>T and 1199G>A, BSEP T>C, MRP2 1249G<A, BCRP T>C and 421C>A, HNF4a 97 C>G, PXR 63396C>T, 7635G>A and 44477A>G, CAR 540C>T and VEGFA -2055A>C and -614A>G SNPs was performed by real-time PCR.
CONCLUSIONS
This preliminary analysis focused on the pharmacogenetic role in lipid toxicity prediction and it could have implications for long-term cardiovascular complications of efavirenz-based treatment.
REFERENCES
Cusato J et al. Int J Antimicrob Agents. 2016
Quercia R et al. Clin Drug Investig. 2015
ACKNOWLEDGMENTS
We thank CoQuaLab ( for its methodological support and assistance in the preparation
and execution of the pharmacokinetic analysis.