一项关于每日使用1%替诺福韦凝胶对足月及近足月妊娠安全性和药代动力学的随机试验。
A randomized safety and pharmacokinetic trial of daily tenofovir 1% gel in term and near-term pregnancy.
作者信息
Beigi Richard H, Noguchi Lisa M, Montgomery Elizabeth, Biggio Joseph, Hendrix Craig W, Marzinke Mark A, Dai James Y, Pan Jason, Kunjara Na Ayudhya Ratiya, Schwartz Jill L, Isaacs Karen, Piper Jeanna M, Watts D Heather
机构信息
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;
出版信息
J Int AIDS Soc. 2016 Sep 21;19(1):20990. doi: 10.7448/IAS.19.1.20990. eCollection 2016.
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 (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%, 0.81). The same was true for newborns in the TFV gel vs placebo arms (4.5% vs 6.3%, 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.
引言
1%的替诺福韦（TFV）阴道凝胶可能会降低HIV-1和单纯疱疹病毒2感染的发生率。怀孕可能会增加感染HIV的风险，孕期感染HIV会增加围产期HIV传播的可能性。我们的目的是研究1%的TFV阴道凝胶在足月和近足月妊娠中使用7天的安全性和药代动力学。
方法
98名健康孕妇被纳入一项2:1随机、双盲、安慰剂对照试验，先分为足月队列，后分为近足月队列。女性连续7天接受TFV或安慰剂凝胶，并在第0天和第6天进行药代动力学采样。分娩时采集母体和脐带血。主要终点包括实验室和生殖器不良事件、不良妊娠和新生儿结局以及母体TFV水平。
结果
大多数不良事件为1级，没有3级或4级不良事件与研究产品相关。两个妊娠队列之间的安全终点没有显著差异（0.18）；因此，将它们的数据合并。随机分配到TFV凝胶组与安慰剂组的母亲的主要安全终点发生率相似（分别为72.7%和68.8%，0.81）。TFV凝胶组与安慰剂组的新生儿情况也是如此（分别为4.5%和6.3%，0.66）。所有随机分配到TFV组的女性在给药后8小时内血清水平均可检测到，第0天和第6天的总体中位数（四分位间距）峰值较低（分别为3.8（2.0至7.0）和5.8（2.6至9.4）ng/mL）。
结论
在足月和近足月妊娠中每日使用1%的TFV阴道凝胶似乎是安全的，且血清药物水平较低。
Zotero 插件