Atazanavir plus low-dose ritonavir in pregnancy: pharmacokinetics and placental transfer

Abstract

Adequate antiretroviral exposure during pregnancy is critical to prevent the vertical transmission of HIV and for maternal health. Pregnancy can alter drug kinetics. We assessed the pharmacokinetics of atazanavir/ritonavir (300/100 mg a day) during pregnancy. An intensive steady-state 24-h pharmacokinetic profile of atazanavir was performed in the third trimester of pregnancy and postpartum. Maternal and umbilical cord blood samples were obtained at delivery. We measured atazanavir by reverse-phase high-performance liquid chromatography. Seventeen women completed the study. Antepartum, the atazanavir geometric mean area under the plasma concentration-time curve from 0 to 24 h (AUC0-24) was 28 510 ng.h/l, the maximum observed plasma concentration (Cmax) was 2 591 ng/ml and the 24-h postdose concentration (Ctrough) was 486 ng/ml. The same postpartum parameters were 30 465 ng.h/l, 2 878 ng/ml and 514 ng/ml, respectively. The antepartum to postpartum ratio for AUC0-24 was 0.94 and for Ctrough was 0.96, indicating equivalence, whereas Cmax values were slightly although not significantly lower. The ratio of cord blood/maternal atazanavir concentration in 14 paired samples was 0.13. Atazanavir exposure during the third trimester of pregnancy is similar to that observed in the non-pregnant period. Over the whole dosing interval, therapeutic drug concentrations well above the wild-type HIV 90% inhibitory concentration are maintained. Atazanavir crosses the placenta, potentially providing further protection for the newborn. As pregnancy does not appear to alter atazanavir exposure, no dose adjustment is required in pregnant women. Results suggest that atazanavir is a reasonable component of HAART during pregnancy.