Atazanavir in pregnancy: impact on neonatal hyperbilirubinemia.

OBJECTIVE: To study the impact on the neonate of maternal antiretroviral therapy with atazanavir (ATV). STUDY DESIGN: An observational study of 22 HIV-infected women receiving, for clinical indications, antiretroviral therapy with ATV 300 mg and ritonavir 100mg during pregnancy and their 23 HIV infants (including a twin pair). RESULTS: Mothers had received ATV for a median duration of 19 months [range 3-49] by delivery. At delivery, plasma HIV-RNA was <40 copies/mL in all patients. Liver enzymes were normal in 19/22 patients, but one woman had grade 3-4 liver toxicity. Maternal serum bilirubin concentrations were above the upper limit of normal in most patients, with grade 3 toxicity in 5 patients. All but one woman had trough ATV concentrations during pregnancy above the minimum effective concentration. The median cord blood ATV concentration was 130 ng/mL [range<30-758]; the cord/maternal ratio was 21%. All neonates were born at term [median 38.2 weeks]. Three neonates had mildly elevated AST transaminase levels. Bilirubin concentrations at birth were significantly higher than maternal concentrations, with a median of 44 µm/L [range 24-129]; values on days 2-3 were 63 [8-212]. Five neonates had jaundice requiring phototherapy, without liver damage, and recovered without sequelae. CONCLUSION: Neonates whose mothers were treated with ATV should be monitored for hyperbilirubinemia, which may be due to placental transfer of unconjugated bilirubin from the mother and/or a direct effect of transplacental ATV on bilirubin metabolism in the fetus.