Predictors of the change in bilirubin levels over twelve weeks of treatment with atazanavir

Introduction Atazanavir (ATV) is a protease inhibitor used in the treatment of HIV infection. It is useful in patients on methadone replacement therapy as its once daily dosing facilitates co-administration with methadone and, unlike the non-nucleoside reverse transcriptase inhibitor, efavirenz, it does not accelerate the metabolism of methadone via induction of cytochrome P450 enzymes [1]. ATV is associated with unconjugated hyperbilirubinaemia in 6-40% of patients, overt jaundice in 7-8% and discontinuation in up to 2% [2,3]. The pathophysiology of ATVhyperbilirubinaemia is analogous to Gilbert’s syndrome; ATV competitively inhibits UDP-glucuronyltransferase (UGT) enzymes leading to reduced glucuronidation of bilirubin and increased levels of unconjugated bilirubin [4,5]. Patients with the UGT1A1*28 genotype are particularly, but not exclusively, vulnerable [6,7]. Our study aimed to determine the clinical predictors of ATV-associated hyperbilirubinaemia in our patient population.