Pharmacokinetics of once-daily darunavir/ritonavir in HIV-1-infected pregnant women

H. M. Crauwels, T. N. Kakuda, B. Ryan, C. Zorrilla, O. O. Osiyemi, Salih Y Yasin, K. Brown, P. Verboven, V. Hillewaert, B. Baugh

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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 14C-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 (AUC24h) for total darunavir was 34-35% lower during pregnancy vs. postpartum. Unbound darunavir AUC24h 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 CD4 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.

Original languageEnglish (US)
JournalHIV Medicine
DOIs
StateAccepted/In press - 2016

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Ritonavir
HIV-1
Pregnant Women
Pharmacokinetics
Pregnancy
Postpartum Period
Antiviral Agents
Darunavir
Mothers
Gestational Diabetes
Third Pregnancy Trimester
Second Pregnancy Trimester
CD4 Lymphocyte Count
Tandem Mass Spectrometry

Keywords

  • HIV
  • Darunavir
  • Once-daily
  • Pharmacokinetics
  • Pregnancy

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)
  • Health Policy

Cite this

Crauwels, H. M., Kakuda, T. N., Ryan, B., Zorrilla, C., Osiyemi, O. O., Yasin, S. Y., ... Baugh, B. (Accepted/In press). Pharmacokinetics of once-daily darunavir/ritonavir in HIV-1-infected pregnant women. HIV Medicine. https://doi.org/10.1111/hiv.12366

Pharmacokinetics of once-daily darunavir/ritonavir in HIV-1-infected pregnant women. / Crauwels, H. M.; Kakuda, T. N.; Ryan, B.; Zorrilla, C.; Osiyemi, O. O.; Yasin, Salih Y; Brown, K.; Verboven, P.; Hillewaert, V.; Baugh, B.

In: HIV Medicine, 2016.

Research output: Contribution to journalArticle

Crauwels, HM, Kakuda, TN, Ryan, B, Zorrilla, C, Osiyemi, OO, Yasin, SY, Brown, K, Verboven, P, Hillewaert, V & Baugh, B 2016, 'Pharmacokinetics of once-daily darunavir/ritonavir in HIV-1-infected pregnant women', HIV Medicine. https://doi.org/10.1111/hiv.12366
Crauwels, H. M. ; Kakuda, T. N. ; Ryan, B. ; Zorrilla, C. ; Osiyemi, O. O. ; Yasin, Salih Y ; Brown, K. ; Verboven, P. ; Hillewaert, V. ; Baugh, B. / Pharmacokinetics of once-daily darunavir/ritonavir in HIV-1-infected pregnant women. In: HIV Medicine. 2016.
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abstract = "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 14C-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 (AUC24h) for total darunavir was 34-35{\%} lower during pregnancy vs. postpartum. Unbound darunavir AUC24h 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 CD4 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.",
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T1 - Pharmacokinetics of once-daily darunavir/ritonavir in HIV-1-infected pregnant women

AU - Crauwels, H. M.

AU - Kakuda, T. N.

AU - Ryan, B.

AU - Zorrilla, C.

AU - Osiyemi, O. O.

AU - Yasin, Salih Y

AU - Brown, K.

AU - Verboven, P.

AU - Hillewaert, V.

AU - Baugh, B.

PY - 2016

Y1 - 2016

N2 - 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 14C-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 (AUC24h) for total darunavir was 34-35% lower during pregnancy vs. postpartum. Unbound darunavir AUC24h 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 CD4 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.

AB - 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 14C-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 (AUC24h) for total darunavir was 34-35% lower during pregnancy vs. postpartum. Unbound darunavir AUC24h 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 CD4 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.

KW - HIV

KW - Darunavir

KW - Once-daily

KW - Pharmacokinetics

KW - Pregnancy

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