Title: Hyperbilirubinemia in atazanavir-treated human immunodeficiency virus-infected patients: the impact of the UGT1A1*28 allele
Authors: Naidoo A, Naidoo K, Ramsuran V, Reddy M, Padayatchi N.
Journal: Pharmacogenomics and Personalized Medicine,:doi: 10.2147/PGPM.S146787 (2017)
Panagopoulos et al reviewed the effects of the UGT1A1*28 polymorphism on Reyataz (atazanavir)-related hyperbilirubinemia in human immunodeficiency virus (HIV)-infected patients that may result in increased severity and drug discontinuation in some patients.
The effects of the UGT1A1 polymorphisms on the pharmacokinetics of other antiretroviral drugs such as Isentress (raltegravir) and Edurant (rilpivirine) are also discussed. We respond here on the relevance of the study findings in the South African context.
The antiretroviral protease inhibitor (PI) atazanavir inhibits hepatic uridine diphosphate- glucuronosyltransferase (UGT) 1A1, thereby preventing the glucuronidation and elimination of bilirubin.2 This may result in hyperbilirubinemia in >50% of patients, with jaundice that can cause premature discontinuation of atazanavir in ~2%?8% of patients.2 Risk for bilirubin-related discontinuation of atazanavir is substantially increased among individuals who carry two TAn repeat polymorphisms within the UGT1A1 loci: TA7 (UGT1A1*28) and TA8 (UGT1A1*37) that reduce gene transcription, with reported positive predictive values for discontinuation ranging from 20% to 60% depending on race or ethnicity.
Citation: Naidoo A, Naidoo K, Ramsuran V, Reddy M, Padayatchi N. Hyperbilirubinemia in atazanavir-treated human immunodeficiency virus-infected patients: the impact of the UGT1A1*28 allele Pharmacogenomics and Personalized Medicine,:doi: 10.2147/PGPM.S146787 (2017).
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