Pharmacokinetics and Safety of Tenofovir in HIV-Infected Women During Labor and Their Infants During the First Week of Life

Mirochnick, Mark; Taha, Taha E.; Kreitchmann, Régis; Nielsen‐Saines, Karin; Kumwenda, Newton; João, Esaú; Pinto, Jorge; Santos, Breno; Parsons, Teresa L.; Kearney, Brian P.; Emel, Lynda; Herron, Casey M.; Richardson, Paul; Hudelson, Sarah E.; Eshleman, Susan H.; George, Kathleen; Fowler, Mary Glenn; Sato, Paul A.; Mofenson, Lynne

doi:10.1097/qai.0b013e3182a921eb

Cited by 57 publications

(51 citation statements)

References 17 publications

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“…The third study included patients administered tenofovir at the onset of labor, excluding any patients who had previously received tenofovir. Patients received a dose of either 600mg (n = 63) or 900mg (n = 36); for both groups the median cord to maternal plasma concentration ratio was 0.6 [16]. …”

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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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%

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

McCormack

Best

2014

Clin Pharmacokinet

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“…In the lactating mother who is receiving TDF, the low amounts of active drug found in breast milk are not absorbed through the baby's GI tract. Hence, treatment of the mother with TDF results in minimal exposure of the fetus and the breastfed infant to active tenofovir 84 85…”

Section: Postpartum Considerations In Hbv-infected Womenmentioning

confidence: 99%

Managing HBV in pregnancy. Prevention, prophylaxis, treatment and follow-up: position paper produced by Australian, UK and New Zealand key opinion leaders

Visvanathan

Dusheiko

Giles

et al. 2015

Gut

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Hepatitis B during pregnancy presents unique management issues for both the mother and fetus. These include the lack of a current cohesive strategy for treatment and follow-up of mothers and their babies; the uncertain risk of postpartum HBV flares; the lack of randomised trial data on the safety and efficacy of antiviral treatment in pregnancy; the lack of head-to-head studies comparing different antivirals in pregnancy; and the lack of epidemiologic information regarding infection across different populations globally. This position paper provides a comprehensive review of the management of women with HBV infection prior to conception, throughout each stage of pregnancy and postpartum, as well as recommendations and clinical approaches for the follow-up of children born to infected mothers, based on available evidence in the literature and recommendations from international experts. Prevention of perinatal transmission is an important component of global efforts to reduce the burden of chronic HBV since vertical transmission is responsible for most of the chronic infection worldwide.

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“…In the study of Pan et al, breastfeeding was banned for mothers taking TDF during the first four weeks after delivery. In HIV-mothers, TDF concentrations in breast milk are reported to be very low, ranging from 17.6 ng/mL to undetectable levels one week after delivery 6 and the median plasma concentration detected in breastfed children at 6 months of age was 24 ng/mL. 7 Examination of breast milk TDF concentration could have been an interesting result that arose from this study, but it was missed.…”

mentioning

confidence: 82%

Antiviral treatment of HBV positive pregnant women: an additional tool to reduce perinatal transmission

Bruni

Taliani

Ciccaglione

2016

Pathogens and Global Health

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In a recent study published in New England Journal of Medicine, Pan and colleagues 1 faced an important aspect for prevention of hepatitis B virus (HBV) infection: antiviral treatment with Tenofovir (TDF) during pregnancy to reduce perinatal transmission. This route of infection plays a crucial role for global diffusion of HBV, with frequency of chronic infection in mother-to-childtransmission (MTCT) of 90%.The results by Pan and colleagues show that TDF treatment during pregnancy significantly reduces the transmission rate compared to the standard prophylaxis recommended by World Health Organization (WHO), 2 that leaves a residual HBV transmission mostly in highly viremic mothers (>200,000 IU/mL HBV-DNA). Thus, reduction of the viral load at delivery by antiviral treatment is an attractive possibility in reducing MTCT. Indeed, in a recent simulation model of the global HBV epidemic, scaling up the use of peripartum antivirals (to 80% of HBeAg positive mothers), together with other interventions, was indicated as an important strategy to avert 7.3 million deaths between 2015 and 2030. 3 Earlier reports have shown conflicting results but, according to recent WHO guidelines, 2 quality scores of some studies were low, highlighting the need for further, more carefully designed ones. Pan et al. performed a multicenter, open-label, randomized, parallel-group study, enrolling 200 highly viremic mothers. The reliability of the results was significantly improved by a proper experimental design. The primary outcomes (transmission rate and birth defects) were assessed at 28 weeks after birth, a longer follow-up than in previous studies. In addition, monitoring of maternal viral load convincingly demonstrated, in 68% mothers, reduction of viremia at delivery below the 200,000 IU/mL, considered to be the threshold value for significant decrease of MTCT.

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Pharmacokinetics and Safety of Tenofovir in HIV-Infected Women During Labor and Their Infants During the First Week of Life

Cited by 57 publications

References 17 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

Managing HBV in pregnancy. Prevention, prophylaxis, treatment and follow-up: position paper produced by Australian, UK and New Zealand key opinion leaders

Antiviral treatment of HBV positive pregnant women: an additional tool to reduce perinatal transmission

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