title: Clinical and pharmacogenetic factors affecting neonatal bilirubinemia following atazanavir treatment of mothers during pregnancy.
abstract: A theoretical concern exists that atazanavir (ATV) use during pregnancy may exacerbate physiologic neonatal hyperbilirubinemia. The aim of this substudy was to evaluate patterns of neonatal bilirubin following ATV/ritonavir (RTV) treatment of pregnant mothers and clinical and pharmacogenetic factors that may correlate. The design involved a subanalysis of study AI424182, a multicenter, open-label, prospective, single-arm Phase I study. The study had two treatment arms: (1) ATV/RTV 300/100 mg once daily or (2) ATV/RTV 400/100 mg once daily, both in combination with zidovudine/lamivudine 300/150 mg twice daily. Total bilirubin was assessed at baseline, each visit, and delivery day for mothers and on days 1 (delivery day), 3, 5, and 7 and weeks 2 and 6 for neonates. Blood samples were obtained for UGT1A1 genotyping and ATV cord blood concentration. Bilirubin elevation of any grade occurred in 14/40 neonates (35%). All Grade 3 to 4 bilirubin abnormalities (n=7) occurred after day 14. The pattern of neonatal bilirubin levels reported was consistent with neonatal physiologic elevations of bilirubin. Little correlation was observed between either maternal bilirubin levels over the last 4 weeks of pregnancy (including delivery) or ATV cord concentration and neonatal bilirubin. There was a significant association between UGT1A1 genotype and bilirubin grade in the maternal population (p=0.0006) but not neonates (p=0.49). Neither neonatal UGT1A1 genotype nor cord blood ATV concentration is a good predictor of neonatal hyperbilirubinemia. ATV/RTV treatment of mothers does not appear to exacerbate neonatal physiologic hyperbilirubinemia.
authors.affiliation: 1 Bristol-Myers Squibb, Research and Development , Hopewell, New Jersey.
authors.forename: Timothy
authors.initials: T
authors.lastname: Eley
authors.forename: Shu-Pang
authors.initials: SP
authors.lastname: Huang
authors.forename: Francesca
authors.initials: F
authors.lastname: Conradie
authors.forename: Carmen D
authors.initials: CD
authors.lastname: Zorrilla
authors.forename: Deirdre
authors.initials: D
authors.lastname: Josipovic
authors.forename: Mariëtte
authors.initials: M
authors.lastname: Botes
authors.forename: Olayemi
authors.initials: O
authors.lastname: Osiyemi
authors.forename: Hélène
authors.initials: H
authors.lastname: Hardy
authors.forename: Richard
authors.initials: R
authors.lastname: Bertz
authors.forename: Donnie
authors.initials: D
authors.lastname: McGrath
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000069446:Atazanavir Sulfate; D001663:Bilirubin / Q000097:blood; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced* / Q000235:genetics*; D007231:Infant, Newborn; D009842:Oligopeptides / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010949:Plasma / Q000737:chemistry; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D011446:Prospective Studies; D011725:Pyridines / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use; D000099148:UGT1A1 Enzyme
chemical_list: D019380:Anti-HIV Agents; D000069446:Atazanavir Sulfate; D001663:Bilirubin; D014453:Glucuronosyltransferase; D009842:Oligopeptides; D011725:Pyridines; D019438:Ritonavir; D000099148:UGT1A1 Enzyme