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

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. Keywords: HIV; pregnancy; prevention; pharmacokinetics; safety; tenofovir. (Published: 21 September 2016) Citation: Beigi RH et al. Journal of the International AIDS Society 2016, 19 :20990 http://www.jiasociety.org/index.php/jias/article/view/20990 | http://dx.doi.org/10.7448/IAS.19.1.20990