Elvitegravir/cobicistat pharmacokinetics in pregnant and postpartum women with HIV. (13th November 2018)

• Record Type: Journal Article
• Authors: Momper, Jeremiah D.; Best, Brookie M.; Wang, Jiajia; Capparelli, Edmund V.; Stek, Alice; Barr, Emily; Badell, Martina L.; Acosta, Edward P.; Purswani, Murli; Smith, Elizabeth; Chakhtoura, Nahida; Park, Kyunghun; Burchett, Sandra; Shapiro, David E.; Mirochnick, Mark
• Is Part Of: AIDS. Volume 32:Number 17(2018)
• Publication Date: 2018-11-13
• Subjects: cobicistat -- elvitegravir -- HIV infection -- integrase inhibitor -- perinatal transmission -- pharmacokinetics -- pregnancy; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000001992
• Languages: English
• ISSNs: 0269-9370

Abstract

Abstract : Objective: To evaluate elvitegravir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples after delivery. Design: Nonrandomized, open-label, parallel-group, multicenter phase-IV prospective study of antiretroviral pharmacokinetics in HIV-infected pregnant women and their children in the United States. Methods: Intensive steady-state 24-h pharmacokinetic profiles after 150 mg of elvitegravir and 150 mg of cobicistat given orally in fixed dose combination once-daily were performed during the second trimester, third trimester, and postpartum. Infant washout samples were collected after birth. Elvitegravir and cobicistat were measured in plasma by a validated liquid chromatography with tandem mass spectrometry assay with a lower quantitation limit of 10 ng/ml. A two-tailed Wilcoxon signed-rank test (α = 0.10) was employed for paired within-participant comparisons. Results: Thirty pregnant women taking elvitegravir and cobicistat once-daily enrolled in the study. Compared with paired postpartum data, elvitegravir AUC0–24 was 24% lower in the second trimester [ n = 14, P = 0.058, geometric mean ratios (GMR) = 0.76, 90% confidence interval (CI) 0.57–1.0] and 44% lower in the third trimester ( n = 24, P = 0.0001, GMR = 0.56, 90% CI 0.42–0.73), while cobicistat AUC0–24 was 44% lower in the second trimester ( n = 14, P = 0.0085, GMR = 0.56, 90% CI 0.37–0.85) and 59% lower in the third trimester ( n = 24, P < 0.0001, GMR = 0.41, 90% CI 0.30–0.57). Median cord blood elvitegravir concentration was 540.6 ng/ml and the median ratio of cord blood to maternal plasma elvitegravir concentrations was 0.91. Conclusion: Standard elvitegravir and cobicistat dosing during pregnancy results in significantly lower exposure which may increase the risk of virologic failure and mother-to-child transmission. Additional studies are needed to optimize elvitegravir and cobicistat dosing regimens in pregnant women.