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

• Published in: HIV medicine Vol. 20; no. 5; pp. 337 - 343
• Main Authors: Crauwels, HM, Osiyemi, O, Zorrilla, C, Bicer, C, Brown, K
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.05.2019
• Subjects: Adult; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Antiviral activity; Antiviral agents; cobicistat; Cobicistat - administration & dosage; Cobicistat - pharmacokinetics; darunavir; Darunavir - administration & dosage; Darunavir - pharmacokinetics; Drug Therapy, Combination; Exposure; Female; Gestation; Gestational Age; HIV; HIV Infections - drug therapy; Human immunodeficiency virus; Humans; Infant, Newborn; Infants; Infectious Disease Transmission, Vertical - statistics & numerical data; Maternal Age; Pharmacokinetics; Pharmacology; Plasma; Postpartum; Postpartum Period - blood; Pregnancy; Pregnancy Complications, Infectious - drug therapy; Pregnancy Trimester, Second - blood; Ribonucleic acid; RNA; Treatment Outcome; pharmacokinetics; darunavir; HIV; cobicistat; pregnancy
• ISSN: 1464-2662; 1468-1293
• DOI: 10.1111/hiv.12721

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 (AUC24 h), maximum plasma concentration (Cmax) and minimum plasma concentration (Cmin)] 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 (AUC24 h, 50–56% lower; Cmax, 37–49% lower; Cmin, 89–92% lower); unbound darunavir exposure was also reduced (AUC24 h, 40–45% lower; Cmax, 32–41% lower; Cmin, 88–92% lower). Cobicistat exposure was also lower during pregnancy than postpartum (AUC24 h, 49–63% lower; Cmax, 27–50% lower; Cmin, 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.