Trial reportHIV medicine2014
Total and unbound darunavir pharmacokinetics in pregnant women infected with HIV-1: results of a study of darunavir/ritonavir 600/100 mg administered twice daily.
Trial report in HIV medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 2 syntheses or guidelines pooled it, 50 citations in OpenAlex.
- Pregnancy-Associated Changes in Pharmacokinetics: A Systematic Review.PLoS medicine · 2016Pooled it
- Protecting the fetus against HIV infection: a systematic review of placental transfer of antiretrovirals.Clinical pharmacokinetics · 2014Pooled it
- Maintenance darunavir/ritonavir monotherapy to prevent perinatal HIV transmission, ANRS-MIE 168 MONOGEST study.The Journal of antimicrobial chemotherapy · 2023Trial
- Evaluation of Cardiovascular Disease Risk in HIV-1-Infected Patients Treated with Darunavir.Drugs in R&D · 2018Trial
- Mechanistic Modeling of Maternal Lymphoid and Fetal Plasma Antiretroviral Exposure During the Third Trimester.Frontiers in pediatrics · 2021Article
- Pharmacokinetic Enhancement of HIV Antiretroviral Therapy During Pregnancy.Journal of clinical pharmacology · 2020Review
- Drug-Drug Interactions with Antiretroviral Drugs in Pregnant Women Living with HIV: Are They Different from Non-Pregnant Individuals?Clinical pharmacokinetics · 2020Review
- Darunavir Pharmacokinetics With an Increased Dose During Pregnancy.Journal of acquired immune deficiency syndromes (1999) · 2020Article
- Corrigendum.HIV medicine · 2019Article
- Low plasmatic concentration of intensified antiretroviral therapy in a pregnant woman: a case report.Journal of medical case reports · 2019Article
- Evaluating darunavir/ritonavir dosing regimens for HIV-positive pregnant women using semi-mechanistic pharmacokinetic modelling.The Journal of antimicrobial chemotherapy · 2019Article
- Pharmacokinetics, Antiviral Activity, and Safety of Rilpivirine in Pregnant Women with HIV-1 Infection: Results of a Phase 3b, Multicenter, Open-Label Study.Infectious diseases and therapy · 2018Article
- Toward a universal antiretroviral regimen: special considerations of pregnancy and breast feeding.Current opinion in HIV and AIDS · 2017Review
- Physiologically Based Modelling of Darunavir/Ritonavir Pharmacokinetics During Pregnancy.Clinical pharmacokinetics · 2016Article
- Pharmacokinetics of Once Versus Twice Daily Darunavir in Pregnant HIV-Infected Women.Journal of acquired immune deficiency syndromes (1999) · 2015Article
- Placental transfer of darunavir in an ex vivo human cotyledon perfusion model.Antimicrobial agents and chemotherapy · 2014Article
- Review
Corrections and comments
- Erratum issuedCorrigendum.2019
Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesAntiretroviral therapy during pregnancy is recommended to reduce the risk of mother-to-child transmission of HIV and for maternal care management. Physiological changes during pregnancy can affect pharmacokinetics, potentially altering pharmacological activity. We therefore evaluated the pharmacokinetics of twice-daily (bid) darunavir in HIV-1-infected pregnant women.
methodsHIV-1-infected pregnant women receiving an antiretroviral regimen containing darunavir/ritonavir 600/100 mg bid were enrolled in this study. Total and unbound darunavir and total ritonavir plasma concentrations were obtained over 12 h during the second and third trimesters and postpartum. Total darunavir and ritonavir plasma concentrations were determined using a validated high-performance liquid chromatography tandem mass spectrometry assay and unbound darunavir was determined using (14) C-darunavir-fortified plasma. Pharmacokinetic parameters were derived using noncompartmental analysis.
resultsData were available for 14 women. The area under the plasma concentration-time curve from 0 to 12 h (AUC12h) for total darunavir was 17-24% lower during pregnancy than postpartum. The AUC12h for unbound darunavir was minimally reduced during pregnancy vs. postpartum. The minimum plasma concentration (Cmin) of total and unbound darunavir was on average 43-86% and 10-14% higher, respectively, during pregnancy vs. postpartum. The antiviral response (< 50 HIV-1 RNA copies/mL) was 33% at baseline and increased to 73-90% during treatment; the percentage CD4 count increased over time. One serious adverse event was reported (increased transaminase). All 12 infants born to women remaining in the study at delivery were HIV-1-negative; four of these infants were premature.
conclusionsTotal darunavir exposure decreased during pregnancy. No clinically relevant change in unbound (active) darunavir occurred during pregnancy, suggesting that no dose adjustment is required for darunavir/ritonavir 600/100 mg bid in pregnant women.
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