Impact of pharmacogenetics on CNS side effects related to efavirenz

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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.

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