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Pharmacogenomics. 2013 Jul;14(10):1167-78. doi: 10.2217/pgs.13.111.

Impact of pharmacogenetics on CNS side effects related to efavirenz.

Author information

1
Pharmacy Service, University Hospital of Salamanca, Salamanca, Spain.

Abstract

AIM:

This article evaluates which genetic factors are involved in CNS toxicity related to long-term treatment with efavirenz (EFV) standard doses and their relationship with plasma concentrations.

PATIENTS & METHODS:

A total of 119 HIV-positive patients, in which 1350 EFV plasma concentrations, 68 SNPs and 14 EFV-related adverse effects (AEs) were analyzed.

RESULTS:

Overall, 32.77% of patients reported CNS toxicity and 8.40% had concentrations above the therapeutic range. A correlation was mainly found between patients with global CNS AEs and high EFV maximum steady-state plasma concentration (p = 1.47 × 10(-6)). A preliminary analysis confirmed that CYP2B6*6 (516G>T and 785A>G) was the most highly correlated (p = 0.005) with AEs and high plasma concentrations. In a second analysis adjusting for maximum steady-state plasma concentration, suggestive genetic associations were found between BCRP 421C>A, MRP1 816G>A, 5-HT2A 102C>T and different AEs.

CONCLUSION:

The finding of the involvement of these SNPs in EFV toxicity opens the door for further studies to confirm their validity and for their application in the future clinical practice. Original submitted 18 February 2013; Revision submitted 17 May 2013.

PMID:
23859571
DOI:
10.2217/pgs.13.111
[Indexed for MEDLINE]

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