Elvitegravir/cobicistat pharmacokinetics in pregnant and postpartum women with HIV.
AIDS. 2018 Aug 20;:
Authors: Momper JD, Best BM, Wang J, Capparelli EV, Stek A, Barr E, Badell ML, Acosta EP, Purswani M, Smith E, Chakhtoura N, Park K, Burchett S, Shapiro DE, Mirochnick M, IMPAACT P1026s Protocol Team
OBJECTIVE: To evaluate elvitegravir and cobicistat pharmacokinetics during pregnancy compared to postpartum and in infant washout samples after delivery.
DESIGN: Nonrandomized, open-label, parallel-group, multi-center phase-IV prospective study of antiretroviral pharmacokinetics in HIV-infected pregnant women and their children in the U.S.
METHODS: Intensive steady-state 24 hour 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 LC-MS/MS 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 to paired postpartum data, elvitegravir AUC0-24 was 24% lower in the second trimester (n = 14, P = 0.058, GMR = 0.76, 90% 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 < .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.
CONCLUSIONS: 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.
PMID: 30134297 [PubMed – as supplied by publisher]