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GTR Home > Conditions/Phenotypes > Atazanavir response

Summary

Atazanavir is an antiretroviral of the protease inhibitor (PI) class that is used to treat human immunodeficiency virus (HIV). Atazanavir is typically given with a pharmacokinetic enhancer such as cobicistat or ritonavir and is prescribed as part of a regimen with other antiretrovirals. Atazanavir inhibits uridine diphosphate glucuronosyltransferase (UGT)1A1 (UGT1A1)- mediated glucuronidation of bilirubin, and causes plasma indirect bilirubin concentrations to increase. Although indirect elevations in bilirubin do not necessarily indicate hepatic injury they may cause jaundice. Specific UGT1A1 mutations that reduce UGT1A1 function, particularly in the homozygous state, may greatly increase the likelihood that a patient prescribed atazanavir will develop hyperbilirubinemia and jaundice, and may increase a patient’s risk of non-adherence. Alternative antiretroviral regiments should be recommended for these patients, unless the reasons to prescribe atazanavir are compelling, or the patient is unconcerned about jaundice. Patients with one decreased function UGT1A1 allele have a much lower likelihood of developing jaundice if prescribed atazanavir and although the likelihood of developing jaundice is low, it is recommended that the possibility be discussed with the patient. Therapeutic recommendations for prescribing atazanavir based on an individual’s UGT1A1 genotype have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website. [from PharmGKB]

Available tests

5 tests are in the database for this condition.

Genes See tests for all associated and related genes

  • Also known as: BILIQTL1, GNT1, HUG-BR1, UDPGT, UDPGT 1-1, UGT1, UGT1A, UGT1A1
    Summary: UDP glucuronosyltransferase family 1 member A1

Therapeutic recommendations

From Medical Genetics Summaries

This section contains excerpted1 information on gene-based dosing recommendations. Neither this section nor other parts of this review contain the complete recommendations from the sources.

2023 Statement from the US Food and Drug Administration (FDA)

Contraindications

Atazanavir capsules are contraindicated… when coadministered with drugs that are highly dependent on CYP3A or UGT1A1 for clearance, and for which elevated plasma concentrations of the interacting drugs are associated with serious and/or life-threatening events […]

Drug interactions

Atazanavir is an inhibitor of CYP3A and UGT1A1. Coadministration of atazanavir and drugs primarily metabolized by CYP3A or UGT1A1 may result in increased plasma concentration of the other drug that could increase or prolong its therapeutic and adverse effects. […]

Atazanavir is a CYP3A4 substrate; therefore, drugs that induce CYP3A4 may decrease atazanavir plasma concentrations and reduce atazanavir's therapeutic effect.

Please review the complete therapeutic recommendations that are located here: (1)

2016 Statement from the Clinical Pharmacogenetics Implementation Consortium (CPIC)

For individuals carrying two UGT1A1 decreased function alleles (i.e., UGT1A1*28/*28, UGT1A1*28/*37, UGT1A1*37/*37, or rs887829 T/T), the likelihood of bilirubin-related atazanavir discontinuation is substantial. Before such individuals are prescribed atazanavir (boosted with either ritonavir or cobicistat), all such patients should be advised about the substantial likelihood of developing jaundice. Prescribing atazanavir to such individuals should generally be avoided unless the patient does not consider jaundice to be a concern, or there are other compelling reasons to prescribe atazanavir.

For individuals carrying fewer than two UGT1A1 decreased function alleles (i.e., *1/*28, *1/*37, *36/*28, *36/*37, rs887829 C/C or rs887829 C/T), the likelihood of bilirubin-related atazanavir discontinuation is low. This risk is extremely low for individuals carrying no UGT1A1 decreased function alleles (i.e., UGT1A1*1/*1, UGT1A1*1/*36, UGT1A1*36/*36, or rs887829 C/C). Among patients with extensive metabolizer UGT1A1 phenotypes it may not be necessary to discuss the possibility of jaundice with atazanavir. This decision about whether to discuss possible jaundice should be based on the clinical situation and provider judgment. If advice is offered, such discussion may note that the likelihood of developing jaundice that would require discontinuation of atazanavir is very low.

Please review the complete therapeutic recommendations that are located here: (4)

1 The FDA labels specific drug formulations. In this excerpt, we have substituted the generic names for any specific drug labels. The FDA may not have labeled all formulations containing the generic drug. Where necessary, certain terms, genes and genetic variants may be corrected in accordance with nomenclature standards. We have provided the full name of abbreviations, shown in square brackets, where necessary.

Practice guidelines

  • PAGAA, 2024
    Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Department of Health and Human Services.

Consumer resources

IMPORTANT NOTE: NIH does not independently verify information submitted to the GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in the GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.