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Abstract

BACKGROUND:

Maternal-to-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 of antiretrovirals 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 US 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-to-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.

Protecting the fetus against HIV infection: a systematic review of


placental transfer of antiretrovirals.