Elvitegravir/cobicistat pharmacokinetics in pregnant and postpartum women with HIV

被引:1
|
作者
Momper, Jeremiah D. [1 ]
Best, Brookie M. [1 ]
Wang, Jiajia [2 ]
Capparelli, Edmund V. [1 ]
Stek, Alice [3 ]
Barr, Emily [4 ]
Badell, Martina L. [5 ]
Acosta, Edward P. [6 ]
Purswani, Murli [7 ]
Smith, Elizabeth [8 ]
Chakhtoura, Nahida [9 ]
Park, Kyunghun [1 ]
Burchett, Sandra [10 ]
Shapiro, David E. [2 ]
Mirochnick, Mark [11 ]
机构
[1] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, 9500 Gilman Dr,MC 0657, La Jolla, CA 92093 USA
[2] Harvard TH Chan Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA USA
[3] Univ Southern Calif, Sch Med, Los Angeles, CA USA
[4] Univ Colorado, Childrens Hosp Colorado, Aurora, CO USA
[5] Emory Univ, Sch Med, Atlanta, GA USA
[6] Univ Alabama Birmingham, Birmingham, AL USA
[7] Icahn Sch Med Mt Sinai, Bronx Lebanon Hosp Ctr, New York, NY 10029 USA
[8] NIAID, Maternal Adolescent & Pediat Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA
[9] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, Bethesda, MD USA
[10] Childrens Hosp Boston, Boston, MA USA
[11] Boston Univ, Sch Med, Boston, MA 02118 USA
基金
美国国家卫生研究院;
关键词
cobicistat; elvitegravir; HIV infection; integrase inhibitor; perinatal transmission; pharmacokinetics; pregnancy; COBICISTAT; EXPRESSION;
D O I
10.1097/QAD.0000000000001992
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 anti retroviral 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 (alpha= 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 AUC(0-24) 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 AUC(0-24) was 44% lower in the second trimester (n = 14, P = 0.0085, GMR = 0.56, 90% CI 0.3 7-0.85) 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. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.
引用
收藏
页码:2507 / 2516
页数:10
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