Therapeutic drug monitoring of atazanavir/ritonavir in pregnancy

OBJECTIVES: Pregnant women experience physiological changes during pregnancy that can have a significant impact on antiretroviral pharmacokinetics. Ensuring optimal plasma concentrations of antiretrovirals is essential for maternal health and to minimize the risk of vertical transmission. Here we describe atazanavir/ritonavir (ATV/r) plasma concentrations in a cohort of pregnant women undergoing routine therapeutic drug monitoring (TDM). METHODS: Pregnant HIV-positive women received ATV/r as part of their routine pre-natal care. Demographic and clinical data were collected. ATV plasma concentrations ([ATV]) were determined in the first (T1), second (T2) and third (T3) trimesters and at postpartum (PP) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: From January 2007, 44 women (37 black African) were enrolled in the study. All received ATV/r at a dose of 300/100 mg once a day. Twenty-four had received antiretroviral therapy (ART) prior to pregnancy, and 20 initiated ATV/r in pregnancy. At the time nearest to delivery, 36 patients had undetectable plasma viral loads. [ATV] values were determined in 11 (T1), 25 (T2), 34 (T3) and 28 (PP) patients. [ATV] at 24 hours post-dose (C24) values significantly lower at T2/T3 relative to PP. CONCLUSIONS: This study was carried out in one of the larger cohorts of women undergoing TDM for ATV in pregnancy. Lower [ATV] values were seen in T2/T3 compared with T1/PP. However, [ATV] were not associated with a lack of virologic suppression at delivery. Nonetheless, careful monitoring of women in pregnancy is required, and dose adjustment of ATV to 400 mg may be an option.