Premium
Reduced exposure to darunavir and cobicistat in HIV ‐1‐infected pregnant women receiving a darunavir/cobicistat‐based regimen
Author(s) -
Crauwels HM,
Osiyemi O,
Zorrilla C,
Bicer C,
Brown K
Publication year - 2019
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/hiv.12721
Subject(s) - cobicistat , darunavir , medicine , pharmacokinetics , regimen , pregnancy , area under the curve , gestation , postpartum period , ritonavir , pharmacology , gastroenterology , human immunodeficiency virus (hiv) , viral load , antiretroviral therapy , virology , biology , genetics
Objectives The aim of the study was to evaluate darunavir and cobicistat pharmacokinetics in pregnant women with HIV ‐1 infection. Methods This phase 3b, open‐label study enrolled HIV ‐1‐infected pregnant women (18–26 weeks of gestation) receiving combination antiretroviral therapy with once‐daily darunavir/cobicistat 800/150 mg. The plasma pharmacokinetics of darunavir (total and unbound) and cobicistat were assessed over 24 h during the second and third trimesters (24–28 and 34–38 weeks of gestation, respectively) and 6–12 weeks postpartum. Pharmacokinetic parameters [area under the plasma concentration–time curve over 24 h ( AUC 24 h ), maximum plasma concentration ( C max ) and minimum plasma concentration ( C min )] were derived using noncompartmental analysis and compared using linear mixed effects modelling (pregnancy versus postpartum). Antiviral activity and safety were evaluated. Results Seven women were enrolled in the study; six completed it. Total darunavir exposure was lower during pregnancy than postpartum ( AUC 24 h , 50–56% lower; C max , 37–49% lower; C min , 89–92% lower); unbound darunavir exposure was also reduced ( AUC 24 h , 40–45% lower; C max , 32–41% lower; C min , 88–92% lower). Cobicistat exposure was also lower during pregnancy than postpartum ( AUC 24 h , 49–63% lower; C max , 27–50% lower; C min , 83% lower). At study completion, five of six (83%) women were virologically suppressed ( HIV ‐1 RNA < 50 copies/ mL ). There was one virological failure (the patient was nonadherent; no emerging genotypic resistance was observed and susceptibility to antiretrovirals was maintained). No mother‐to‐child transmission was detected among six infants born to the six women who completed the study. Overall, darunavir/cobicistat was well tolerated in women and infants. Conclusions In view of markedly reduced darunavir and cobicistat exposures during pregnancy, this combination is not recommended in HIV ‐1‐infected pregnant women.