A randomized safety and pharmacokinetic trial of daily tenofovir 1% gel in term and near-term pregnancy

Richard H. Beigi, Lisa M. Noguchi, Elizabeth Montgomery, Joseph Biggio, Craig Hendrix, Mark A Marzinke, James Y. Dai, Jason Pan, Ratiya Kunjara Na Ayudhya, Jill L. Schwartz, Karen Isaacs, Jeanna M. Piper, D. Heather Watts

Research output: Contribution to journalArticle

Abstract

Introduction: 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.

Original languageEnglish (US)
Article number20990
JournalJournal of the International AIDS Society
Volume19
Issue number1
DOIs
StatePublished - 2016

Keywords

  • HIV
  • Pharmacokinetics
  • Pregnancy
  • Prevention
  • Safety
  • Tenofovir

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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  • Cite this

    Beigi, R. H., Noguchi, L. M., Montgomery, E., Biggio, J., Hendrix, C., Marzinke, M. A., Dai, J. Y., Pan, J., Kunjara Na Ayudhya, R., Schwartz, J. L., Isaacs, K., Piper, J. M., & Watts, D. H. (2016). A randomized safety and pharmacokinetic trial of daily tenofovir 1% gel in term and near-term pregnancy. Journal of the International AIDS Society, 19(1), [20990]. https://doi.org/10.7448/IAS.19.1.20990