Screening for UGT1A1 Genotype in Study A5257 Would Have Markedly Reduced Premature Discontinuation of Atazanavir for Hyperbilirubinemia.

TitleScreening for UGT1A1 Genotype in Study A5257 Would Have Markedly Reduced Premature Discontinuation of Atazanavir for Hyperbilirubinemia.
Publication TypeJournal Article
Year of Publication2015
AuthorsVardhanabhuti S, Ribaudo HJ, Landovitz RJ, Ofotokun I, Lennox JL, Currier JS, Olson LM, Haas DW
JournalOpen Forum Infect Dis
Volume2
Issue3
Paginationofv085
Date Published2015 Sep
ISSN2328-8957
Abstract

Background.  Some patients are not prescribed atazanavir because of concern about possible jaundice. Atazanavir-associated hyperbilirubinemia correlates with UGT1A1 rs887829 genotype. We examined bilirubin-related discontinuation of atazanavir in participants from AIDS Clinical Trials Group Study A5257. Methods.  Discriminatory properties of UGT1A1 T/T genotype for predicting bilirubin-related atazanavir discontinuation through 96 weeks after antiretroviral initiation were estimated. Results.  Genetic analyses involved 1450 participants, including 481 who initiated randomized atazanavir/ritonavir. Positive predictive values of rs887829 T/T for bilirubin-related discontinuation of atazanavir (with 95% confidence intervals [CIs]) were 20% (CI, 9%-36%) in Black, 60% (CI, 32%-84%) in White, and 29% (CI, 8%-58%) in Hispanic participants; negative predictive values were 97% (CI, 93%-99%), 95% (CI, 90%-98%), and 97% (CI, 90%-100%), respectively. Conclusions.  Bilirubin-related discontinuation of atazanavir was rare in participants not homozygous for rs887829 T/T, regardless of race or ethnicity. We hypothesize that the higher rate of discontinuation among White participants homozygous for rs887829 T/T may reflect differences in physical manifestations of jaundice by race and ethnicity. Selective avoidance of atazanavir initiation among individuals with T/T genotypes would markedly reduce the likelihood of bilirubin-related discontinuation of atazanavir while allowing atazanavir to be prescribed to the majority of individuals. This genetic association will also affect atazanavir/cobicistat.

DOI10.1093/ofid/ofv085
Alternate JournalOpen Forum Infect Dis
PubMed ID26180834
PubMed Central IDPMC4498287
Grant ListP30 AI110527 / AI / NIAID NIH HHS / United States
R01 AI077505 / AI / NIAID NIH HHS / United States
U01 AI069418 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069418 / AI / NIAID NIH HHS / United States
UM1 AI069439 / AI / NIAID NIH HHS / United States