title: Impact of UGT1A1 Gilbert variant on discontinuation of ritonavir-boosted atazanavir in AIDS Clinical Trials Group Study A5202.
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%).
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Ribaudo
authors.forename: Eric S
authors.initials: ES
authors.lastname: Daar
authors.forename: Camlin
authors.initials: C
authors.lastname: Tierney
authors.forename: Gene D
authors.initials: GD
authors.lastname: Morse
authors.forename: Katie
authors.initials: K
authors.lastname: Mollan
authors.forename: Paul E
authors.initials: PE
authors.lastname: Sax
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Fischl
authors.forename: Ann C
authors.initials: AC
authors.lastname: Collier
authors.forename: David W
authors.initials: DW
authors.lastname: Haas
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D000069446:Atazanavir Sulfate; D001663:Bilirubin / Q000097:blood; D014644:Genetic Variation; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D007565:Jaundice / Q000453:epidemiology; D009842:Oligopeptides; D011725:Pyridines; D019438:Ritonavir / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D014453:Glucuronosyltransferase; D019438:Ritonavir; D001663:Bilirubin