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

Colbers, Angela; Hawkins, David; Gingelmaier, Andrea; Kabeya, Kabamba; Rockstroh, Jürgen K.; Wyen, C.; Weizsäcker, Katharina; Sadiq, S Tariq; Ivanović, Jelena; Giaquinto, Carlo; Taylor, Graham; Moltó, José; Burger, David M.

doi:10.1097/qad.0b013e32835c208b

Cited by 68 publications

(95 citation statements)

References 39 publications

(46 reference statements)

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“…Of the three emtricitabine studies, the geometric mean ratio of cord to maternal plasma concentration was 1.2 in one study (n = 11); for this study the median time between dosing and delivery was 19 hours [13]. For the other emtricitabine study (n = 10), the median cord to maternal ratio was 1.6 but the median time between dosing and delivery was 8.5 hours [14]. For an emtricitabine case report (n = 1) the ratio was 1.7 at 13 hours after dosing [15].…”

Section: Resultsmentioning

confidence: 99%

“…Two studies and a case report all included patients at steady-state, yet the median cord to maternal plasma concentration ratio varied from 0.82 (range 0.64-1.1, n=14) [14] in one study to 6.0 (range 3.5-7.2, n =3) [10] for the other; the case report (n = 1) was in between with a ratio of 1.1 [15]. Data for differences in time elapsed post-dose were not available for comparison.…”

Section: Resultsmentioning

confidence: 99%

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Protecting the Fetus Against HIV Infection: A Systematic Review of Placental Transfer of Antiretrovirals

McCormack

Best

2014

Clin Pharmacokinet

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Background Maternal-fetal transfer of antiretroviral drugs contributes to prevention of vertical transmission of HIV. Objective This systematic review discusses published studies containing data pertaining to the pharmacokinetics of placental transfer in humans, including paired cord and maternal plasma samples collected at the time of delivery as well as ex vivo placental perfusion models. Methods Articles pertaining to placental transfer of antiretrovirals were identified from PubMed, from references of included articles, and from U.S. Department of Health and Human Services Panel on Treatment of HIV-infected Pregnant Women and Prevention of Perinatal Transmission guidelines. Articles from non-human animal models or that had no original maternal-fetal transfer data were excluded. PRISMA guidelines were followed. Results A total of 103 published studies were identified. Data across studies appeared relatively consistent for the nucleoside reverse transcriptase inhibitors (NRTIs) and the non-nucleotide reverse transcriptase inhibitors (NNRTIs), with cord to maternal ratios approaching 1 for many of these agents. The protease inhibitors atazanavir and lopinavir exhibited consistent maternal-to-fetal transfer across studies, although the transfer may be influenced by variations in drug-binding proteins. The protease inhibitors indinavir, nelfinavir, and saquinavir exhibited unreliable placental transport, with cord blood concentrations that were frequently undetectable. Limited data, primarily from case reports, indicate that darunavir and raltegravir provide detectable placental transfer. Conclusion These findings appear consistent with current guidelines of using two NRTIs plus an NNRTI, atazanavir/ritonavir, or lopinavir/ritonavir to maximize placental transfer as well as to optimally suppress maternal viral load. Darunavir/ritonavir and raltegravir may reasonably serve as second-line agents.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Protecting the Fetus Against HIV Infection: A Systematic Review of Placental Transfer of Antiretrovirals

McCormack

Best

2014

Clin Pharmacokinet

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“…Previous studies have demonstrated placental transfer, with drug concentrations approaching 1 g/ml in maternal and cord blood ratios for certain nucleoside (or nucleotide) reverse transcriptase inhibitors (NRTIs) (15)(16)(17)32) with slightly lower ratios reported for non-NRTIs (18)(19)(20) and even lower ratios for the protease inhibitors (16,21). Studies analyzing placental transfer of TFV have reported variable results, with maternal and cord blood concentration ratios ranging from 0.82 to 6.0 (16,18).…”

Section: Discussionmentioning

confidence: 99%

“…Studies analyzing placental transfer of TFV have reported variable results, with maternal and cord blood concentration ratios ranging from 0.82 to 6.0 (16,18). Protease inhibitors, such as atazanavir (22,23) and lopinavir (20,24) actively cross the placenta; however, undetectable concentrations in cord blood have been reported for nelfinavir, indinavir, and saquinavir (25,26).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Placental Transfer of Elvitegravir, Dolutegravir, and Other Antiretrovirals during Pregnancy

Rimawi

Johnson

Rajakumar

et al. 2017

Antimicrob Agents Chemother

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The integrase inhibitors elvitegravir (EVG) and dolutegravir (DTG) rapidly decrease the plasma HIV-1 viral load, a key factor in the prevention of maternal-tofetal transmission of HIV-1. No data have been reported on the concentrations of these drugs in cord blood, maternal peripheral blood mononuclear cells (PBMCs), or placental tissue in pregnant women. We present in vivo pharmacokinetic data on antiretrovirals (ARV) within maternal and cord blood and within placentae from HIV-1-infected pregnant women. Maternal blood and cord blood were obtained from women receiving EVG, cobicistat, tenofovir disoproxil fumarate, and emtricitabine as a single fixed-dose combination formulation or DTG as part of a combination regimen. Plasma and PBMCs from maternal and cord blood were obtained along with villous placental samples. Drug concentrations were simultaneously determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Utilizing medians and ranges to interpret our data, we compared the drug concentration ratios between different matrices (maternal and cord blood plasma, PBMCs, and placenta). All five agents transferred from maternal into fetal circulation via the placenta. Concentration ratios for EVG, cobicistat, tenofovir, and emtricitabine (n ϭ 10) and DTG (n ϭ 3) were determined between cord plasma and placenta, cord and maternal plasma, and cord PBMCs and maternal PBMCs. TFV moves from maternal plasma through the placenta to the cord blood and then into cord PBMCs, where it is phosphorylated into its active forms (TFV diphosphate). These five ARVs were detected in each of the compartments, highlighting transfer of these agents from the maternal into the fetal circulation.

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“…A similar European study also found no significant association overall between intrapartum intravenous AZT and MTCT, though it did not evaluate by viral load [17]. On the basis of a number of human studies [18][19][20], there does not seem to be any need for dose adjustment to maintain adequate drug levels for NRTIs in pregnancy. There is a trial in progress to assess women participating in a pre-exposure prophylaxis study who are taking TDF based therapies and become pregnant [21].…”

Section: Nucleos(t)ide Reverse Transcriptase Inhibitors (Nrti)mentioning

confidence: 98%

HIV and Pregnancy

Vogler

2014

Curr Treat Options Infect Dis

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

Abstract: 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.

Cited by 68 publications

References 39 publications

Protecting the Fetus Against HIV Infection: A Systematic Review of Placental Transfer of Antiretrovirals

Protecting the Fetus Against HIV Infection: A Systematic Review of Placental Transfer of Antiretrovirals

Pharmacokinetics and Placental Transfer of Elvitegravir, Dolutegravir, and Other Antiretrovirals during Pregnancy

HIV and Pregnancy

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