Atazanavir in pregnancy: impact on neonatal hyperbilirubinemia

Eur J Obstet Gynecol Reprod Biol. 2011 Jul;157(1):18-21. doi: 10.1016/j.ejogrb.2011.02.005. Epub 2011 Apr 13.

Abstract

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiretroviral Therapy, Highly Active / adverse effects
  • Atazanavir Sulfate
  • Bilirubin / blood
  • Cohort Studies
  • Female
  • Fetal Blood
  • HIV Infections / drug therapy
  • HIV Protease Inhibitors / adverse effects*
  • HIV Protease Inhibitors / blood
  • HIV Protease Inhibitors / therapeutic use
  • Humans
  • Hyperbilirubinemia, Neonatal / blood
  • Hyperbilirubinemia, Neonatal / chemically induced*
  • Infant, Newborn
  • Jaundice, Neonatal / blood
  • Jaundice, Neonatal / chemically induced
  • Jaundice, Neonatal / therapy
  • Male
  • Maternal-Fetal Exchange
  • Medical Records
  • Oligopeptides / adverse effects*
  • Oligopeptides / blood
  • Oligopeptides / therapeutic use
  • Phototherapy
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy
  • Prenatal Exposure Delayed Effects* / blood
  • Pyridines / adverse effects*
  • Pyridines / blood
  • Pyridines / therapeutic use
  • Retrospective Studies
  • Ritonavir / therapeutic use

Substances

  • HIV Protease Inhibitors
  • Oligopeptides
  • Pyridines
  • Atazanavir Sulfate
  • Ritonavir
  • Bilirubin