title: Protecting the fetus against HIV infection: a systematic review of placental transfer of antiretrovirals.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pediatrics Department-Rady Children's Hospital, University of California San Diego, La Jolla, CA, USA.
authors.forename: Shelley A
authors.initials: SA
authors.lastname: McCormack
authors.forename: Brookie M
authors.initials: BM
authors.lastname: Best
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D005333:Fetus / Q000821:virology; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control* / Q000635:transmission; D019428:HIV Integrase Inhibitors / Q000493:pharmacokinetics; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008431:Maternal-Fetal Exchange; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000517:prevention & control*; D011760:Pyrrolidinones / Q000494:pharmacology / Q000627:therapeutic use; D000068898:Raltegravir Potassium; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D019438:Ritonavir / Q000494:pharmacology / Q000627:therapeutic use; D014481:United States
chemical_list: D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors; D011760:Pyrrolidinones; D018894:Reverse Transcriptase Inhibitors; D000068898:Raltegravir Potassium; D019438:Ritonavir