An overview of genetic variants regarding efavirenz‐related dysthymias in HIV‐infected patients: Response to a letter to the editor

• Published in: Clinical cardiology (Mahwah, N.J.) Vol. 45; no. 4; pp. 329 - 330
• Main Authors: Hosseini, Zahra, Tayeb, Roya, Ghodsi, Saeed, Sadre Bafghi, Seyed‐Ali, Mollazadeh, Reza
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.04.2022; John Wiley and Sons Inc
• Subjects: Alkynes - therapeutic use; Anti-HIV Agents - adverse effects; Antiretroviral drugs; Benzoxazines - adverse effects; Cyclopropanes - therapeutic use; Haplotypes; HIV; HIV Infections - diagnosis; HIV Infections - drug therapy; Human immunodeficiency virus; Humans; Liver
• ISSN: 0160-9289; 1932-8737
• DOI: 10.1002/clc.23789

[...]several studies have examined the association of these genetic markers with plasma levels of EFV as well as subsequent adverse effects. Since EFV may prolong QT interval through inhibition of delayed rectifier potassium current (IKr), coded via human Ether-a-go-go-Related Gene, certain CYP2B6 variants may increase this hazard accordingly. 3 The locus of CYP2B6 is characterized with multiple variations subtending 38 known different alleles, haplotypes and diverse single nucleotide polymorphisms. 4 In addition to genetic heterogeneity, allelic variations including multiple CYP2B6 polymorphisms may also contribute to altered pharmacokinetics of EFV. 5 The CYP2B6*1 and CYP2B6*2 alleles convey normal function whereas CYP2B6*6 is assigned as a decreased function haplotype. [...]genetic assays pertaining to the CYP2B6*6 allele are presumably not sufficient to delineate major pharmacogenetic determinants of EFV-related dysrhythmias. [...]controversy surrounds the diagnostic utility of the CYP2B6*6 allele in guiding the treatment of HIV-infected patients who receive EFV.