Background:  Optimal ART exposure during pregnancy is critical to preventing mother-to-child transmission (MTCT) of HIV. Pregnancy can alter ART pharmacokinetics. Our objective was to describe atazanavir/ritonavir (ATV/r) pharmacokinetics during pregnancy.

Methods:  We performed intensive steady-state 24-hour pharmacokinetic profiles of ATV/r associated with zidovudine (AZT) and lamivudine (3TC) (at standard doses) at 30 to 36 weeks gestation and 8 to 16 weeks post-partum. Maternal and umbilical cord blood samples were obtained at delivery. High-performance liquid chromatography (HPLC) was used to measure ATV/r concentrations.

Results:  For the 9 women who completed ante- and post-partum evaluations (see the figure), their mean age was 31 years and their mean baseline CD4 count was 471 cells/µL. HAART was started between 0 and 24 weeks of pregnancy (mean 13.7). The mean antepartum ATV/r AUC was 29.4 µg·h/mL (SE 3.1), while the post-partum value was 33.5 µg·h/ml (SE 3.8) with a mean ante- to post-partum ratio of 0.95 (SD 0.34). Ante-partum ATV/r mean C_max resulted of 2.7 µg/mL (SE 0.4) compared to a post-partum value of 2.9 µg/mL (SE 0.4) for a ante- to post-partum ratio of 1.03 (SD 0.31).  T_max was of 3.1 h ante-partum and 2.8 h post-partum, while C_min resulted of 5.2 µg/mL ante-partum and 5.9 µg/mL post-partum. None of the considered measures was significantly different (p >0.05) nor were they influenced by the women’s body mass index (mean 26.9 during and 24.5 after pregnancy). ATV/r mean concentration in the cord blood at delivery was 0.22 µg/mL (SD 0.13) and counted for 9.7% of the concomitant maternal blood concentration 2.3 µg/mL (SD 1.3). All newborns at delivery and 3 months after birth resulted HIV RNA negative. None of them required phototherapy.

Conclusions:  Despite a quite large inter-patient variability, ATV/r concentrations during late pregnancy were similar to those obtained post-partum. No dose adjustments should be needed. Small amounts of ATV cross the placenta. An ATV/r-based HAART is effective in preventing MTCT of HIV infection.