Cargando…

Race/ethnicity difference in the pharmacogenetics of bilirubin-related atazanavir discontinuation

BACKGROUND: Atazanavir causes plasma indirect bilirubin to increase. We evaluated associations between Gilbert’s polymorphism and bilirubin-related atazanavir discontinuation stratified by race/ethnicity. PATIENTS AND METHODS: Patients had initiated atazanavir/ritonavir-containing regimens at an HIV...

Descripción completa

Detalles Bibliográficos
Autores principales: Leger, Paul, Chirwa, Sanika, Nwogu, Jacinta N., Turner, Megan, Richardson, Danielle M., Baker, Paxton, Leonard, Michael, Erdem, Husamettin, Olson, Lana, Haas, David W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726942/
https://www.ncbi.nlm.nih.gov/pubmed/29117017
http://dx.doi.org/10.1097/FPC.0000000000000316
Descripción
Sumario:BACKGROUND: Atazanavir causes plasma indirect bilirubin to increase. We evaluated associations between Gilbert’s polymorphism and bilirubin-related atazanavir discontinuation stratified by race/ethnicity. PATIENTS AND METHODS: Patients had initiated atazanavir/ritonavir-containing regimens at an HIV primary care clinic in the southeastern USA, and had at least 12 months of follow-up data. Metabolizer group was defined by UGT1A1 rs887829 C→T. Genome-wide genotype data were used to adjust for genetic ancestry in combined population analyses. RESULTS: Among 321 evaluable patients, 15 (4.6%) had bilirubin-related atazanavir discontinuation within 12 months. Homozygosity for rs887829 T/T was present in 28.1% of Black, 21.4% of Hispanic, and 8.6% of White patients. Among all patients the hazard ratio (HR) for bilirubin-related discontinuation with T/T versus C/C genotype was 7.3 [95% confidence interval (CI): 1.7–31.5; P=0.007]. Among 152 White patients the HR was 14.4 (95% CI: 2.6–78.7; P=0.002), but among 153 Black patients the HR was 0.8 (95% CI: 0.05–12.7; P=0.87). CONCLUSION: Among patients who initiated atazanavir/ritonavir-containing regimens, UGT1A1 slow metabolizer genotype rs887829 T/T was associated with increased bilirubin-related discontinuation of atazanavir in White but not in Black patients, this despite T/T genotype being more frequent in Black patients.