Transplacental transfer of atazanavir and neonatal hyperbilirubinaemia

Results from a study evaluating the transplacental transfer of atazanavir (ATV) and the incidence of hyperbilirubinaemia in ATV exposed neonates were presented at the 14th International Workshop on Clinical Pharmacology.

In this analysis, foetal cord blood of 16 (15 pregnancies with one set of twins) in utero exposed infants were evaluated for ATV and bilirubin concentrations. The investigators then compared these to maternal levels at time of delivery. Neonatal bilirubin levels in the first 24 hours of life were also collected.

Of the mothers, six were receiving ATV before conception and nine started treatment between 19 and 33 weeks gestation. Most (13/15) women were virologically suppressed <50 copies/mL at delivery. The infants weighed a mean of 3.3 kg (range 2.0-4.7) at birth. The twins were born pre-term at 35 weeks and the remainder of infants were born at >37 gestation.

The investigators noted considerable variability in maternal ATV concentrations at delivery but suggested this was most likely to be due to the differences in time of sampling since last dose. Median ATV concentration was 1250 ng/mL (range <48 – 34441); 13/15 were above than the MEC of 150 ng/mL. Detectable ATV levels were observed in 12/15 cord blood samples, median 223 ng/mL (range <48 – 531), 8 were above the MEC and three were borderline.

Linear regression analysis revealed a significant association between maternal and cord blood ATV concentrations, R2 = 0.632, p<0.001. The mean ratio of maternal to cord blood concentration was 0.14 (95% CI 0.08-0.20).

Median maternal serum total bilirubin concentration at delivery was 23.5 mmoL/mL (range 6 – 102); median cord blood total bilirubin concentration was 34mmoL/mL (range 15- 89) and median neonatal total bilirubin concentration was 60 mmoL/mL (range 19 – 146).

One infant with an indirect bilirubin level of 146mmoL/mL at 27 hours of age was excluded from the analysis. Among the remaining infants, investigators reported a significant correlation between neonatal unconjugated bilirubin concentration and both maternal serum unconjugated bilirubin and cord unconjugated bilirubin concentrations, respectively R2=0.693, p=0.02 and R2=0.759, p=<0.001. They observed no correlation between ATV level and bilirubin concentrations. There were no cases of hyperbilirubinaemia.

They noted that transplacental transfer of ATV might offer additional protection to the neonate from vertical transmission of HIV, with therapeutic levels observed in most of the cord blood samples in this study.

Lambert J et al. Transplacental passage of atazanavir and neonatal hyperbilirubinaemia. 14th International Workshop on Clinical Pharmacology. 22-24 April 2013. Amsterdam. Poster abstract P_16.