title: A randomized safety and pharmacokinetic trial of daily tenofovir 1% gel in term and near-term pregnancy.
abstract: BACKGROUND
  Vaginal tenofovir (TFV) 1% gel may reduce incident HIV-1 and herpes simplex virus 2 infection. Pregnancy may increase risk of HIV acquisition, and incident HIV in pregnancy potentiates perinatal HIV transmission. Our objective was to investigate the safety and pharmacokinetics of seven days of TFV 1% vaginal gel in term and near-term pregnancy.
  
  
  METHODS
  Ninety-eight healthy pregnant women, stratified to a term cohort followed by a near-term cohort, were enrolled into a 2:1 randomized, double-blinded, placebo-controlled trial. Women received TFV or placebo gel for seven consecutive days with pharmacokinetic sampling on days 0 and 6. Maternal and cord blood were collected at delivery. Primary end points included laboratory and genital adverse events, adverse pregnancy and neonatal outcomes, and maternal TFV levels.
  
  
  RESULTS
  Most adverse events were grade 1 and none of the grade 3 or 4 adverse events were related to study product. There was no significant difference in safety end points between the two pregnancy cohorts (p=0.18); therefore, their data were combined. Primary safety end point rates were similar for mothers randomized to the TFV gel vs placebo arm (72.7 and 68.8%,p=0.81). The same was true for newborns in the TFV gel vs placebo arms (4.5% vs 6.3%,p=0.66). All women randomized to TFV had quantifiable serum levels within eight hours of dosing, with low overall median (interquartile range) day 0 and day 6 peak values (3.8 (2.0 to 7.0) and 5.8 (2.6 to 9.4) ng/mL, respectively).
  
  
  CONCLUSIONS
  Daily TFV 1% vaginal gel use in term and near-term pregnancy appears to be safe and produces low serum drug levels.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Hospital of UPMC, Pittsburgh, PA, USA.|Microbicide Trials Network, Magee-Womens Research Institute, Pittsburgh, PA, USA; rbeigi@mail.magee.edu.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Beigi
authors.affiliation: Microbicide Trials Network, Magee-Womens Research Institute, Pittsburgh, PA, USA.|Department of Medicine, Clinical Pharmacology, The Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Noguchi
authors.affiliation: RTI International, San Francisco, CA, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Montgomery
authors.affiliation: Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Biggio
authors.affiliation: Department of Medicine, Clinical Pharmacology, The Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Craig W
authors.initials: CW
authors.lastname: Hendrix
authors.affiliation: Department of Medicine, Clinical Pharmacology, The Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Marzinke
authors.affiliation: Statistical Center for HIV/AIDS Research and Prevention, Seattle, WA, USA.
authors.forename: James Y
authors.initials: JY
authors.lastname: Dai
authors.affiliation: Statistical Center for HIV/AIDS Research and Prevention, Seattle, WA, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Pan
authors.affiliation: Microbicide Trials Network, Magee-Womens Research Institute, Pittsburgh, PA, USA.
authors.forename: Ratiya
authors.initials: R
authors.lastname: Kunjara Na Ayudhya
authors.affiliation: Department of Obstetrics and Gynecology, CONRAD/Eastern Virginia Medical School, Arlington, VA, USA.
authors.forename: Jill L
authors.initials: JL
authors.lastname: Schwartz
authors.affiliation: Pharmetrics, Chapel Hill, NC, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Isaacs
authors.affiliation: Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
authors.forename: Jeanna M
authors.initials: JM
authors.lastname: Piper
authors.affiliation: Office of the Global AIDS Coordinator and Health Diplomacy, US Department of State, Washington, DC, USA.
authors.forename: D Heather
authors.initials: DH
authors.lastname: Watts
keywords: HIV; pharmacokinetics; pregnancy; prevention; safety; tenofovir