PANNA

15

Oct, 2017

Lowered Rilpivirine Exposure During the Third Trimester of Pregnancy in Human Immunodeficiency Virus Type 1-Infected Women

 

Authors: Schalkwijk S, Colbers A, Konopnicki D, et al.

Published in: Clin Infect Dis. 2017; 65(8):1335-1341.

Background The use of antiretroviral therapy during pregnancy is important for control of maternal human immunodeficiency virus (HIV) disease and the prevention of perinatal HIV transmission. Physiological changes during pregnancy can reduce antiretroviral exposure. We studied the pharmacokinetics of rilpivirine 25 mg once daily in HIV-1–infected women during late pregnancy.
Methods We conducted a nonrandomized, open-label, multicenter, phase 4 study. HIV-infected pregnant women receiving rilpivirine 25 mg once daily were included. Intensive 24-hour pharmacokinetic sampling was performed in the third trimester and at least 2 weeks postpartum. Pharmacokinetic parameters were calculated by noncompartmental analysis.
Results Sixteen subjects were included. Geometric mean ratios of third trimester vs postpartum were 0.55 (90% confidence interval [CI], .46–.66) for the 24-hour area under the concentration-time curve (AUC0-24h); 0.65 (90% CI, .55–.76) for the maximum concentration; and 0.51 (90% CI, .41–.63) for the minimum observed concentration (Cmin). Four of 16 (25%) subjects had Cmin below the target concentration (0.04 mg/L) in the third trimester of pregnancy. No subtherapeutic levels were observed postpartum. No detectable viral loads were observed in this study. All newborns tested negative for HIV. No birth defects were reported. The median (range, n = 5) rilpivirine cord-to-maternal plasma concentration ratio was 0.50 (range, .35–.81).
Conclusions Rilpivirine exposure is substantially lowered during late pregnancy. Despite lower exposure, virologic suppression was maintained and no perinatal transmission was observed. Overall, these results suggest that rilpivirine 25 mg once daily may be an alternative treatment option for HIV-1–infected pregnant women who are virologically suppressed, in settings where therapeutic drug monitoring and/or close viral load monitoring are feasible to detect suboptimal antiretroviral therapy.
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4

Aug, 2016

Etravirine Pharmacokinetics in HIV-Infected Pregnant Women

 

Authors: Blonk MI, Colbers AP, HidalgoTenorio C, et al.

Published inFront Pharmacol. 2016 Aug 4;7:239.

Background: The study goal was to describe etravirine pharmacokinetics during pregnancy and postpartum in HIV-infected women.

Methods: IMPAACT P1026s and PANNA are on-going, non-randomized, open-label, parallel-group, multi-center phase-IV prospective studies in HIV-infected pregnant women. Intensive steady-state 12-h pharmacokinetic profiles were performed from 2nd trimester through postpartum. Etravirine was measured at two labs using validated ultra performance liquid chromatography (detection limits: 0.020 and 0.026 mcg/mL).

Results: Fifteen women took etravirine 200 mg twice-daily. Etravirine AUC0–12 was higher in the 3rd trimester compared to paired postpartum data by 34% (median 8.3 vs. 5.3 mcg*h/mL, p = 0.068). Etravirine apparent oral clearance was significantly lower in the 3rd trimester of pregnancy compared to paired postpartum data by 52% (median 24 vs. 38 L/h, p = 0.025). The median ratio of cord blood to maternal plasma concentration at delivery was 0.52 (range: 0.19–4.25) and no perinatal transmission occurred.

Conclusion: Etravirine apparent oral clearance is reduced and exposure increased during the third trimester of pregnancy. Based on prior dose-ranging and safety data, no dose adjustment is necessary for maternal health but the effects of etravirine in utero are unknown. Maternal health and infant outcomes should be closely monitored until further infant safety data are available.

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31

Jul, 2016

Substantially lowered dolutegravir exposure in a treatment-experienced perinatally HIV-1-infected pregnant woman

 

Authors: Schalkwijk S, Feiterna-Sperling C, Weizsacker K, et al.

Published in: AIDS. 2016; 30(12):1999-2001.

 

No Abstract available

15

May, 2016

The pharmacokinetics of abacavir 600 mg once daily in HIV-1-positive pregnant women

 

Authors: Schalkwijk S, Colbers A, Konopnicki D, et al. For PANNA network

Published inAIDS. 2016;30(8):1239-44.

Objective To describe the pharmacokinetics of abacavir 600 mg once daily (q.d.) in HIV-1-positive women during pregnancy and postpartum.

Design A nonrandomized, open-label, multicentre, phase-IV study.

Methods HIV-positive pregnant women receiving abacavir 600 mg q.d. as part of clinical care were included. Intensive 24-h pharmacokinetic sampling was performed during the third trimester and at least 2 weeks after delivery. Pharmacokinetic parameters were calculated by noncompartmental analysis. Paired cord blood and maternal blood samples were taken at delivery when feasible.

Results A total of 14 women were included in the analysis. Geometric mean ratios (90% confidence intervals) of third trimester versus postpartum were 1.05 (0.92–1.19) for AUC0–24h and 1.00 (0.83–1.21) for Cmax. The median (range) ratio of abacavir cord plasma to maternal plasma was 1.0 (0.7–1.0, n = 3). Viral load at the third trimester visit was less than 50 copies/ml in 13 participants (93%; one unknown). In total, 13 (93%; one unknown) children were tested HIV-negative.

Conclusion The pharmacokinetics of abacavir 600 mg q.d. during pregnancy are equivalent to postpartum. No dose adjustments are required during pregnancy and similar antiviral activity is expected.

13

Mar, 2016

First reported use of elvitegravir and cobicistat during pregnancy

 

Authors: Schalkwijk S, Colbers A, Konopnicki D, Greupink R, Russel FG, Burger D; PANNA network.

Published inAIDS. 2016;30(5):807-8.

Abstract not available

1

Sep, 2015

Raltegravir in HIV-1 Infected Pregnant Women: Pharmacokinetics, Safety, and Efficacy

 

Authors: Blonk MI, Colbers AP, Hidalgo-Tenorio C, et al. Pharmacokinetics of Newly Developed Antiretroviral Agents in HIV-Infected Pregnant Women PANNA Network; PANNA Network.

Published in: Clin Infect Dis. 2015; 61(5):809-816. 

BackgroundThe use of raltegravir in human immunodeficiency virus (HIV)–infected pregnant women is important in the prevention of mother-to-child HIV transmission, especially in circumstances when a rapid decline of HIV RNA load is warranted or when preferred antiretroviral agents cannot be used. Physiological changes during pregnancy can reduce antiretroviral drug exposure. We studied the effect of pregnancy on the pharmacokinetics of raltegravir and its safety and efficacy in HIV-infected pregnant women.

Methods An open-label, multicenter, phase 4 study in HIV-infected pregnant women receiving raltegravir 400 mg twice daily was performed (Pharmacokinetics of Newly Developed Antiretroviral Agents in HIV-Infected Pregnant Women Network). Steady-state pharmacokinetic profiles were obtained in the third trimester and postpartum along with cord and maternal delivery concentrations. Safety and virologic efficacy were evaluated.

Results Twenty-two patients were included, of which 68% started raltegravir during pregnancy. Approaching delivery, 86% of the patients had an undetectable viral load (<50 copies/mL). None of the children were HIV-infected. Exposure to raltegravir was highly variable. Overall area under the plasma concentration-time curve (AUC) and plasma concentration at 12 hours after intake (C12h) plasma concentrations in the third trimester were on average 29% and 36% lower, respectively, compared with postpartum: Geometric mean ratios (90% confidence interval) were 0.71 (.53–.96) for AUC0–12h and 0.64 (.34–1.22) for C12h. The median ratio of raltegravir cord to maternal blood was 1.21 (interquartile range, 1.02–2.17; n = 9).

Conclusions Raltegravir was well tolerated during pregnancy. The pharmacokinetics of raltegravir showed extensive variability. The observed mean decrease in exposure to raltegravir during third trimester compared to postpartum is not considered to be of clinical importance. Raltegravir can be used in standard dosages in HIV-infected pregnant women.

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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.

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

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

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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 inAntivir Ther. 2015; 20(1):57-64

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

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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.

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