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Pharmacokinetics of once‐daily darunavir/ritonavir in HIV ‐1–infected pregnant women
Author(s) -
Crauwels HM,
Kakuda TN,
Ryan B,
Zorrilla C,
Osiyemi OO,
Yasin S,
Brown K,
Verboven P,
Hillewaert V,
Baugh B
Publication year - 2016
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.12366
Subject(s) - darunavir , medicine , ritonavir , pregnancy , postpartum period , pharmacokinetics , regimen , pharmacology , viral load , human immunodeficiency virus (hiv) , immunology , antiretroviral therapy , biology , genetics
Objectives HIV antiretroviral therapy during pregnancy is recommended to reduce the risk of mother‐to‐child transmission and for maternal care. Physiological changes during pregnancy can affect pharmacokinetics. The impact of pregnancy was evaluated for once‐daily (qd) darunavir/ritonavir. Methods HIV ‐1–infected pregnant women on an antiretroviral regimen that includes darunavir were enrolled in the study and further treated with darunavir/ritonavir 800/100 mg qd. Plasma concentrations were assessed over 24 h during the second and third trimesters and postpartum using a validated high‐performance liquid chromatography tandem mass spectrometry assay for total darunavir and ritonavir, and using 14 C‐darunavir–fortified plasma for unbound darunavir. Pharmacokinetic parameters were derived using noncompartmental analysis. Safety and antiviral response were assessed at all visits. Results Data were available for 16 women. The area under the plasma concentration–time curve from 0 to 24 h ( AUC 24h ) for total darunavir was 34–35% lower during pregnancy vs . postpartum. Unbound darunavir AUC 24h was 20–24% lower during pregnancy vs . postpartum. The minimum plasma concentration of total and unbound darunavir was 32–50% and 13–38% lower, respectively, during pregnancy vs . postpartum. The antiviral response (< 50 HIV ‐1 RNA copies/ mL ) was 59% at baseline and increased to 87–100% during the trial; the CD 4 count increased over time. One serious adverse event (gestational diabetes) was judged as possibly related to study medication. All 16 infants born to women remaining in the study at delivery were HIV‐1 negative (two were premature). Conclusions Total darunavir exposure decreased during pregnancy, but the decrease was less for unbound (active) darunavir. These changes are not considered clinically relevant. Darunavir/ritonavir 800/100 mg qd may therefore be a treatment option for HIV ‐1–infected pregnant women.