Elvitegravir/cobicistat pharmacokinetics in pregnant and postpartum women with HIV.
AIDS
; 32(17): 2507-2516, 2018 11 13.
Article
em En
| MEDLINE
| ID: mdl-30134297
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 150âmg of elvitegravir and 150âmg 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 10âng/ml. A two-tailed Wilcoxon signed-rank test (αâ=â0.10) 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 [nâ=â14, Pâ=â0.058, geometric mean ratios (GMR)â=â0.76, 90% confidence interval (CI) 0.57-1.0] and 44% lower in the third trimester (nâ=â24, Pâ=â0.0001, GMRâ=â0.56, 90% CI 0.42-0.73), while cobicistat AUC0-24 was 44% lower in the second trimester (nâ=â14, Pâ=â0.0085, GMRâ=â0.56, 90% CI 0.37-0.85) and 59% lower in the third trimester (nâ=â24, Pâ<â0.0001, GMRâ=â0.41, 90% CI 0.30-0.57). Median cord blood elvitegravir concentration was 540.6âng/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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Complicações Infecciosas na Gravidez
/
Gravidez
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Infecções por HIV
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Quinolonas
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Fármacos Anti-HIV
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Período Pós-Parto
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Cobicistat
Tipo de estudo:
Clinical_trials
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Observational_studies
/
Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Middle aged
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Newborn
País como assunto:
America do norte
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article