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Atazanavir

Antiretrovirals

Drug Overview

Atazanavir is a protease inhibitor antiretroviral medication marketed under brand names such as Reyataz and Evotaz.

It is used in combination with other agents for the treatment of HIV-1 infection to suppress viral replication and maintain immune function.

Atazanavir works by inhibiting the HIV-1 protease enzyme, preventing the cleavage of viral polyproteins and resulting in noninfectious viral particles.

Relevant Genes and Their Roles

One key gene affecting atazanavir response is UGT1A1. UGT1A1 encodes the enzyme UDP-glucuronosyltransferase 1A1, which attaches a glucuronic acid molecule to bilirubin and certain drugs to help the body eliminate them.

Genetic variations in UGT1A1 can alter enzyme activity, leading to different metabolizer phenotypes. Reduced activity variants can slow bilirubin clearance and increase the risk of drug-related hyperbilirubinemia (jaundice).

Impact of Genetics on Drug Response

Individuals with reduced or absent UGT1A1 activity experience higher bilirubin levels when taking atazanavir, increasing the risk of jaundice and potential treatment discontinuation, while normal or enhanced activity results in lower risk and standard drug handling; unknown genotypes default to standard dosing with clinical monitoring.

Expected Clinical Effects of Genetic Variation

Ultra-rapid/Rapid Metabolizer

  • Effect on drug levels: Lower bilirubin levels than average
  • Clinical consequence: Minimal risk of hyperbilirubinemia
  • Side effects: No known additional side effects

Normal Metabolizer

  • Effect on drug levels: Expected (reference) bilirubin levels
  • Clinical consequence: Very low likelihood of developing jaundice
  • Side effects: Typical side effect profile; rare mild bilirubin elevations

Intermediate Metabolizer

  • Effect on drug levels: Moderate increase in bilirubin levels
  • Clinical consequence: Low likelihood of jaundice-related discontinuation
  • Side effects: Possible mild jaundice; usually transient and well-tolerated

Poor Metabolizer

  • Effect on drug levels: Markedly elevated bilirubin levels
  • Clinical consequence: High likelihood of jaundice and treatment discontinuation
  • Side effects: Pronounced jaundice (yellowing of eyes/skin); may be severe

Indeterminate/Not Available

  • Effect on drug levels: Unknown
  • Clinical consequence: No specific guidance; follow standard dosing
  • Side effects: Not well characterized

Dosing Guidelines

The following dosing guidelines are based on the available guidelines for atazanavir and UGT1A1 from CPIC.

UGT1A1 Dosing Guideline

Phenotype Clinical Consequence Guideline Recommendation
Normal Metabolizer Reference UGT1A1 activity; very low likelihood of bilirubin-related discontinuation of atazanavir. There is no need to avoid prescribing of atazanavir based on UGT1A1 genetic test result.
Intermediate Metabolizer Somewhat decreased UGT1A1 activity; low likelihood of bilirubin-related discontinuation of atazanavir. There is no need to avoid prescribing of atazanavir based on UGT1A1 genetic test result. Inform the patient that some patients stop atazanavir because of jaundice (yellow eyes and skin), but that this patient’s genotype makes this unlikely
Poor Metabolizer Markedly decreased UGT1A1 activity; high likelihood of bilirubin-related discontinuation of atazanavir. Consider an alternative agent particularly where jaundice would be of concern to the patient.
Indeterminate / Not available Unknown impact Initiate standard starting dose

Alternative Treatment Options

For patients identified as poor metabolizers (high risk of hyperbilirubinemia), consider alternative antiretroviral agents such as darunavir, lopinavir, or integrase inhibitors. These examples are drawn from CPIC guidance and are provided for informational purposes only.

Sources and References

Disclaimer: This document is for informational purposes only and is not a substitute for medical advice. Clinical decisions should be made by a qualified healthcare professional.

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