PANNA

22

Jul, 2015

Maraviroc Pharmacokinetics in HIV-1-Infected Pregnant Women

 

Authors: Colbers A, Best B, Schalkwijk S, et al. PANNA Network and the IMPAACT 1026 Study Team.

Published in: Clin Infect Dis. 2015; 61(10):1582-1589.

Objective To describe the pharmacokinetics of maraviroc in human immunodeficiency virus (HIV)–infected women during pregnancy and post partum.

Methods HIV-infected pregnant women receiving maraviroc as part of clinical care had intensive steady-state 12-hour pharmacokinetic profiles performed during the third trimester and ≥2 weeks after delivery. Cord blood samples and matching maternal blood samples were taken at delivery. The data were collected in 2 studies: P1026 (United States) and PANNA (Europe). Pharmacokinetic parameters were calculated.

Results Eighteen women were included in the analysis. Most women (12; 67%) received 150 mg of maraviroc twice daily with a protease inhibitor, 2 (11%) received 300 mg twice daily without a protease inhibitor, and 4 (22%) had an alternative regimen. The geometric mean ratios for third-trimester versus postpartum maraviroc were 0.72 (90% confidence interval, .60–.88) for the area under the curve over a dosing interval (AUCtau) and 0.70 (0.58–0.85) for the maximum maraviroc concentration. Only 1 patient showed a trough concentration (Ctrough) below the suggested target of 50 ng/mL, both during pregnancy and post partum. The median ratio of maraviroc cord blood to maternal blood was 0.33 (range, 0.03–0.56). The viral load close to delivery was <50 copies/mL in 13 women (76%). All children were HIV negative at testing.

Conclusions Overall maraviroc exposure during pregnancy was decreased, with a reduction in AUCtau and maximum concentration of about 30%. Ctroughwas reduced by 15% but exceeded the minimum Ctrough target concentration. Therefore, the standard adult dose seems sufficient in pregnancy.

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1

Feb, 2015

Pharmacokinetics of total and unbound darunavir in HIV-1-infected pregnant women

 

Authors: Colbers A, Molto J, Ivanovic J, et al. PANNA Network

Published in: J Antimicrob Chemother. 2015; 70(2):534-542

Objectives To describe the pharmacokinetics of darunavir in pregnant HIV-infected women in the third trimester and post-partum.

Patients and Methods This was a non-randomized, open-label, multicentre, Phase IV study in HIV-infected pregnant women recruited from HIV treatment centres in Europe. HIV-infected pregnant women treated with darunavir (800/100 mg once daily or 600/100 mg twice daily) as part of their combination ART were included. Pharmacokinetic curves were recorded in the third trimester and post-partum. A cord blood sample and maternal sample were collected. The study is registered at ClinicalTrials.gov under number NCT00825929.

Results Twenty-four women were included in the analysis [darunavir/ritonavir: 600/100 mg twice daily (n=6); 800/100 mg once daily (n=17); and 600/100 mg once daily (n=1)]. Geometric mean ratios of third trimester versus post-partum (90% CI) were 0.78 (0.60-1.00) for total darunavir AUC0-tau after 600/100 mg twice-daily dosing and 0.67 (0.56-0.82) for total darunavir AUC0-tau after 800/100 mg once-daily dosing. The unbound fraction of darunavir was not different during pregnancy (12%) compared with post-partum (10%). The median (range) ratio of darunavir cord blood/maternal blood was 0.13 (0.08-0.35). Viral load close to delivery was <300 copies/mL in all but two patients. All children were tested HIV-negative and no congenital abnormalities were reported.

Conclusions Darunavir AUC and Cmax were substantially decreased in pregnancy for both darunavir/ritonavir regimens. This decrease in exposure did not result in mother-to-child transmission. For antiretroviral-naive patients, who are adherent, take darunavir with food and are not using concomitant medication reducing darunavir concentrations, 800/100 mg of darunavir/ritonavir once daily is adequate in pregnancy. For all other patients 600/100 mg of darunavir/ritonavir twice daily is recommended during pregnancy.

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1

Jan, 2015

Atazanavir exposure is effective during pregnancy regardless of tenofovir use

 

Authors: Colbers A, Hawkins D, HidalgoTenorio C, et al.

Published in: Antivir Ther. 2015; 20(1):57-64

Background We studied the effect of pregnancy on atazanavir pharmacokinetics in the presence and absence of tenofovir.

Methods This was a non-randomized, open-label, multicentre Phase IV study in HIV-infected pregnant women recruited from European HIV treatment centres. HIV-infected pregnant women treated with boosted atazanavir (300/100 mg or 400/100 mg atazanavir/ritonavir) as part of their combination antiretroviral therapy (cART) were included in the study. 24 h pharmacokinetic curves were recorded in the third trimester and postpartum. Collection of a cord blood and maternal sample at delivery was optional.

Results 31 patients were included in the analysis, 21/31 patients used tenofovir as part of cART. Median (range) gestational age at delivery was 39 weeks (36-42). Approaching delivery 81% (25 patients) had an HIV viral load <50 copies/ml, all <1,000 copies/ml. Least squares means ratios (90% CI) of atazanavir pharmacokinetic parameters third trimester/postpartum were: 0.66 (0.57, 0.75) for AUC0-24h, 0.70 (0.61, 0.80) for Cmax and 0.59 (0.48, 0.72) for C24h. No statistical difference in pharmacokinetic parameters was found between patients using tenofovir versus no tenofovir. None of the patients showed atazanavir concentrations <0.15 mg/l (target for treatment-naive patients). One baby had a congenital abnormality, which was not likely to be related to atazanavir/ritonavir use. None of the children were HIV-infected.

Conclusions Despite 34% lower atazanavir exposure during pregnancy, atazanavir/ritonavir 300/100 mg once daily generates effectiveconcentrations for protease inhibitor (PI)-naive patients, even if co-administered with tenofovir. For treatment-experienced patients (with relevant PI resistance mutations) therapeutic drug monitoring of atazanavir should be considered to adapt the atazanavir/ritonavir dose on an individual basis

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30

Dec, 2014

Pharmacokinetics, safety and transplacental passage of rilpivirine in pregnancy: two cases

 

Authors: Colbers A,  Gingelmaier A, van der Ende M, Rijnders, B, Burger D.

Published in: AIDS 2014;28(2): 288-290

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30

Aug, 2014

Effective exposure to atazanavir during pregnancy, regardless of tenofovir use

 

Authors:  Colbers A, Hawkins D, Hidalgo-Tenorio C, van der Ende M, Kabeya K, Gingelmaier A, Weizsäcker K, Lambert J, Rockstroh J, Burger D; on behalf of the PANNA network

Published: 23rd Conference on Retroviruses and Opportunistic Infections, March 3rd-6th 2014, Boston. P_892

 

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30

Aug, 2014

A comparison of the pharmacokinetics of raltegravir during pregnancy and postpartum

 

Authors: Blonk M, Colbers A, Hidalgo-Tenorio C, Weizsäcker K, Moltó J, Hawkins D, van der Ende M, Gingelmaier A, Taylor G, Burger D; on behalf of the PANNA network

Published: 23rd Conference on Retroviruses and Opportunistic Infections, March 3rd-6th 2014, Boston. P_890

 

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30

Aug, 2014

Low darunavir exposure during pregnancy with 800/100mg darunavir/r QD dosing

 

Authors: Colbers A, Moltó J, Ivanovic J, Hawkins D, Sadiq T, Kabeya K,  Gingelmaier A, Weizsäcker K, Taylor G, Burger D; on behalf of the PANNA network

Published: 23rd Conference on Retroviruses and Opportunistic Infections, March 3rd-6th 2014, Boston. P_887

 

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30

Aug, 2013

A comparison of the pharmacokinetics of maraviroc during pregnancy and postpartum

 

Authors:  Colbers A, Brookie B, Wang J, Stek A, Hidalgo-Tenorio C, Hawkins D, Taylor G, Capparelli E, Burger D, Mirochnick M; on behalf of the PANNA network

Published: 20th Conference on Retroviruses and Opportunistic Infections, March 3rd-6th 2013, Atlanta. P_931

 

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13

Mar, 2013

The pharmacokinetics, safety and efficacy of tenofovir and emtricitabine in HIV-1-infected pregnant women

 

Authors: Colbers AP, Hawkins DA, Gingelmaier A, et al.

Published in: Aids. 2013; 27(5):739-748.

Objective To describe the pharmacokinetics of tenofovir and emtricitabine in the third trimester of pregnant HIV-infected women and at postpartum.

Design A nonrandomized, open-label, multicentre phase IV study in HIV-infected pregnant women recruited from HIV treatment centres in Europe.

Methods HIV-infected pregnant women treated with the nucleotide/nucleoside analogue reverse transcriptase inhibitors (NRTIs) tenofovirdisoproxil fumarate (TDF 300 mg; equivalent to 245 mg tenofovir disoproxil) and/or emtricitabine (FTC 200 mg) were included in the study. Twenty-four-hour pharmacokinetic curves were recorded in the third trimester (preferably week 33) and postpartum (preferably week 4-6). Collection of a cord blood sample and maternal sample at delivery was optional. Pharmacokinetic parameters were calculated using WinNonlin software version 5.3. Statistical analysis was conducted using SPSS version 16.0.

Results Thirty-four women were included in the analysis. Geometric mean ratios of third trimester vs. postpartum [90% confidence interval (CI)] were 0.77 (0.71-0.83) for TDF area under the curve (AUC0-24 h); 0.81 (0.68-0.96) for TDF Cmax and 0.79 (0.70-0.90) for TDF C24 h and 0.75 (0.68-0.82) for FTC AUC0-24 h; and 0.87 (0.77-0.99) for FTC Cmax and 0.77 (0.52-1.12) for FTC C24 h. The viral load close to delivery was less than 200  copies/ml in all but one patient, the average gestational age at delivery was 38 weeks. All children were tested HIV-negative and no congenital abnormalities were reported.

Conclusion Although pharmacokinetic exposure of the NRTIs TDF and FTC during pregnancy is approximately 25% lower, this was not associated with virological failure in this study and did not result in mother-to-child transmission.

30

Aug, 2012

A comparison of the pharmacokinetics of tenofovir during pregnancy and post-partum

 

Authors: Colbers A, Taylor G, Moltó J, Ivanovic J, Wyen C, Schwarze-Zander C, Weizsäcker K, Gingelmaier A, Hawkins D, Sadiq T, Kabamba K, Burger D; on behalf of the PANNA network

Published: 13th International Workshop on Clinical Pharmacology of HIV Therapy, 2012 April 16th-18th, Barcelona

 

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