Pharmacokinetics of darunavir and cobicistat in pregnant and postpartum women with HIV.
AIDS
; 35(8): 1191-1199, 2021 07 01.
Article
em En
| MEDLINE
| ID: mdl-34076612
ABSTRACT
OBJECTIVE:
To evaluate darunavir 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 darunavir and cobicistat pharmacokinetics in pregnant women with HIV and their children in the United States.METHODS:
Intensive steady-state 24-h pharmacokinetic profiles were performed after administration of 800âmg of darunavir and 150âmg of cobicistat orally in fixed dose combination once-daily during the second trimester, third trimester, and postpartum. Infant washout samples were collected after birth. Darunavir and cobicistat were measured in plasma by validated HPLC-UV and liquid chromatography with tandem mass spectrometry detection (LC-MS)/MS assays, respectively. A two-tailed Wilcoxon signed-rank test (αâ=â0.10) was employed for paired within-participant comparisons.RESULTS:
A total of 29 pregnant women receiving darunavir and cobicistat once-daily enrolled in the study. Compared with paired postpartum data, darunavir AUC0--24 was 53% lower in the second trimester [nâ=â12, Pâ=â0.0024, geometric mean of ratio (GMR)=0.47, 90% confidence interval (CI) 0.33 - 0.68] and 56% lower in the third trimester (nâ=â18, Pâ<â0.0001, GMRâ=â0.44, 90% CI 0.36 - 0.54), whereas cobicistat AUC0--24 was 50% lower in the second trimester (nâ=â12, Pâ=â0.0024, GMRâ=â0.50, 90% CI 0.36-0.69) and 56% lower in the third trimester (nâ=â18, Pâ<â0.0001, GMRâ=â0.44, 90% CI 0.35-0.55). Placental transfer of darunavir and cobicistat was limited.CONCLUSION:
Standard darunavir/cobicistat dosing during pregnancy results in significantly lower exposure during pregnancy, which may increase the risk of virologic failure and perinatal transmission.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
Fármacos Anti-HIV
Tipo de estudo:
Clinical_trials
/
Observational_studies
/
Risk_factors_studies
Limite:
Child
/
Female
/
Humans
/
Pregnancy
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article