Theoretically, a persistence of very high maternal bilirubin levels might disrupt the normal transplacental flow of fetal bilirubin, leading to intrauterine hyperbilirubinaemia. The actual threshold of maternal bilirubin level and the duration of elevation required to disrupt normal transplacental flow are unknown, selleck chemicals llc and data are limited to case studies with conflicting results [27–30]. This study had a conservative rule whereby a maternal bilirubin level of 10 mg/dL at any time or a level of 7.5

mg/dL persisting for 2 weeks mandated discontinuation of the study drug. However, this rule was not invoked during the study. Overall the rate of grade 3–4 hyperbilirubinaemia observed in this study was, as expected because of the reduced

ATV exposures in pregnancy, lower than observed in studies of ATV/r 300/100 mg in nonpregnant adults; for example, in study AI424089, grade 3–4 bilirubinaemia was 59% [31], in contrast to the 30% observed in the current study. This study found a weak correlation between maternal bilirubin, both on the day of delivery and over the 4 weeks prior to delivery, and infant bilirubin. Although cord blood concentrations of ATV were <20% of the plasma concentrations on average, the free drug concentrations in the fetus were, as noted, higher than in the mothers at similar Trichostatin A clinical trial total (bound+free) ATV concentrations [26]. While the ATV that crossed the placenta may have inhibited fetal UGT1A1, the placental transport system and maternal elimination of fetal bilirubin appeared to be adequate to deal with any elevated fetal bilirubin. The observed pattern of infant bilirubin was generally consistent with the neonatal physiological elevations of bilirubin. Six infants (15%) did undergo phototherapy; however, infant jaundice and phototherapy are not rare. In fact, about 60% of otherwise healthy term infants will experience jaundice and about 10% of them will require some form of treatment (phototherapy

or exchange transfusions) O-methylated flavonoid [32,33]. Regarding safety overall for the infants, only three serious adverse events were reported as related to drugs used in the study, with the drug implicated being zidovudine, and only two serious adverse events were hepatobiliary (hyperbilirubinaemia and jaundice). The majority of serious adverse events (12 of 14) experienced by infants whose mother received ATV/r 300/100 mg were unlikely to be, or were not, related to the study medication. Regarding efficacy, the selection of a suitable threshold can be controversial; maintaining a plasma concentration of protease inhibitors above a certain threshold appears to be correlated with positive outcome. The US Department of Health and Human Services Treatment guidelines suggest a minimum ATV Cmin of 150 ng/mL if therapeutic drug monitoring is to be used [34].