Impact of UGT1A1 Gilbert variant on discontinuation of ritonavir-boosted atazanavir in AIDS Clinical Trials Group Study A5202.

TitleImpact of UGT1A1 Gilbert variant on discontinuation of ritonavir-boosted atazanavir in AIDS Clinical Trials Group Study A5202.
Publication TypeJournal Article
Year of Publication2013
AuthorsRibaudo HJ, Daar ES, Tierney C, Morse GD, Mollan K, Sax PE, Fischl MA, Collier AC, Haas DW
Corporate AuthorsDS Clinical Trials Group
JournalJ Infect Dis
Volume207
Issue3
Pagination420-5
Date Published2013 Feb 1
ISSN1537-6613
KeywordsAnti-HIV Agents, Antiretroviral Therapy, Highly Active, Atazanavir Sulfate, Bilirubin, Genetic Variation, Genotype, Glucuronosyltransferase, HIV Infections, HIV-1, Humans, Jaundice, Oligopeptides, Pyridines, Ritonavir
Abstract

The UGT1A1*28 variant has been associated with hyperbilirubinemia and atazanavir discontinuation. Protocol A5202 randomly assigned human immunodeficiency virus type 1 (HIV-1)-infected patients to receive atazanavir/ritonavir (atazanavir/r) or efavirenz, with tenofovir/emtricitabine or abacavir/lamivudine. A total of 646 atazanavir/r recipients were evaluable for UGT1A1. Homozygosity for *28/*28 was present in 8% of whites, 24% of blacks, and 18% of Hispanics and was associated with increased bilirubin concentrations. There was an association between *28/*28 and increased atazanavir/r discontinuation among Hispanic participants (P = .005) but not among white or black participants (P = .79 and P = .46, respectively). The positive predictive value of 28*/28* for atazanavir/r discontinuation among Hispanic participants was only 32% (95% confidence interval, 16%-52%).

DOI10.1093/infdis/jis690
Alternate JournalJ. Infect. Dis.
PubMed ID23148286
PubMed Central IDPMC3537445
Grant ListAI-025859 / AI / NIAID NIH HHS / United States
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