Therapeutic drug monitoring of atazanavir/ritonavir in pregnancy

• Published in: HIV medicine Vol. 15; no. 10; pp. 604 - 610
• Main Authors: Else, LJ, Jackson, V, Brennan, M, Back, DJ, Khoo, SH, Coulter‐Smith, S, Lambert, JS
• Format: Journal Article
• Language: English
• Published: England 01.11.2014
• Subjects: Adult; Analysis of Variance; Anti-HIV Agents - pharmacokinetics; Anti-HIV Agents - therapeutic use; atazanavir; Atazanavir Sulfate; Drug Monitoring; Female; HIV Infections - blood; HIV Infections - drug therapy; HIV Protease Inhibitors - pharmacokinetics; HIV Protease Inhibitors - therapeutic use; Humans; Oligopeptides - pharmacokinetics; Oligopeptides - therapeutic use; pharmacokinetics; Pregnancy; Pregnancy Complications, Infectious - blood; Pregnancy Complications, Infectious - drug therapy; Pyridines - pharmacokinetics; Pyridines - therapeutic use; Ritonavir - pharmacokinetics; Ritonavir - therapeutic use; therapeutic drug monitoring; Young Adult; pharmacokinetics; atazanavir; therapeutic drug monitoring; pregnancy
• ISSN: 1464-2662; 1468-1293
• DOI: 10.1111/hiv.12164

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.