Reduced exposure to darunavir and cobicistat in HIV-1-infected pregnant women receiving a darunavir/cobicistat-based regimen.

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 ), maximum plasma concentration (C ) and minimum plasma concentration (C )] 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 , 50-56% lower; C , 37-49% lower; C , 89-92% lower); unbound darunavir exposure was also reduced (AUC , 40-45% lower; C , 32-41% lower; C , 88-92% lower). Cobicistat exposure was also lower during pregnancy than postpartum (AUC , 49-63% lower; C , 27-50% lower; C , 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.