Background:  Elevated serum bilirubin and liver toxicity have been reported among adult patients receiving atazanavir (ATV), but the implications for ART in pregnancy are largely unknown. We evaluated the effect of in utero ATV exposure on neonates.

Methods:  A retrospective, single-center cohort study of 9 infants (7 singletons and twins) born to HIV-infected women exposed to boosted ATV during pregnancy. Laboratory evaluations included complete blood count, bilirubin and transaminase concentrations at birth and follow-up and duration time of ART exposure. Neonatal jaundice was assessed by measurement of transcutaneous bilirubin and serum bilirubin.

Results:  All of the women were taking ATV before becoming pregnant, with a median duration of 13.5 months therapy (range 12 to 27) by delivery. Plasma HIV RNA levels were <40 copies/mL during pregnancy and delivery in all patients; the median CD4⁺ cell count at delivery was 459/µL. The median maternal serum total bilirubin concentration was 26 µM/L (12 to 54). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were normal in 7 of 8 patients, but in 1 woman liver enzymes reached 10 times the normal value in the third trimester of pregnancy (AST 303, ALT 456 IU/mL). The median residual ATV concentration was 619 ng/mL during pregnancy, with a large inter-individual variation (range, 82 to 1985) and was 710 ng/mL (300 to 890) at delivery. Cord blood ATV concentrations were 152 ng/mL (undetectable to 350), a median cord/maternal ratio of 21% (range, 0 to 39%). For neonates, mean birth weight was 3850 g (2230 to 3510) and gestational age was 38.1 weeks (37 to 40). Transaminase levels were normal at birth and at day 3. Total bilirubin concentrations were above normal at birth and day 3, 46 µM/L (22 to 64) and 55 µM/L (22 to 212), respectively; 3 newborns had transient neonatal jaundice without requiring phototherapy.

Conclusions:  ATV-related hyperbilirubinemia does not seem to be increased among pregnant HIV⁺ women. However, placental transfer of total serum bilirubin in neonates was above normal range of reported rates in the general paediatric population. This elevation might be due to free bilirubin placental transfer.