Atazanavir Therapy and UGT1A1 Genotype

Excerpt

Atazanavir is indicated for managing human immunodeficiency virus (HIV) infection as part of a multi-drug regimen (1). While it was once widely recommended as a first-line therapy, it is now primarily suggested as a second-line therapeutic option due to potential adverse effects leading to discontinuation of therapy (2, 3). Atazanavir can cause hyperbilirubinemia (not associated with liver injury) leading to jaundice, which is a common cause of drug discontinuation. Individuals with 2 decreased-function alleles for UGT1A1 are most likely to experience jaundice leading to atazanavir discontinuation, although this can occur despite the individual having a reference UGT1A1 genotype (4). The Clinical Pharmacogenetics Implementation Consortium (CPIC) recommends that when an individual is a known UGT1A1 poor metabolizer, an alternative therapy should be considered particularly when jaundice is of concern to the individual (Table 1) (4). The US Food and Drug Administration (FDA) approved drug label states that certain comedications that depend upon UGT1A1 or the cytochrome P450 family member CYP3A are contraindications for atazanavir therapy due to the potential for elevated plasma concentrations of these comedications (1).