Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh.
Magee-Womens Research Institute, Pittsburgh, Pennsylvania.
Clin Infect Dis. 2019 Mar 19;68(7):1144-1151. doi: 10.1093/cid/ciy654.
Postmenopausal women have unique sociobiological human immunodeficiency virus (HIV) risks. We evaluated the safety, pharmacokinetics, and acceptability of a microbicide dapivirine (DPV) vaginal ring (VR) versus placebo in postmenopausal women.
We enrolled 96 HIV-negative postmenopausal US women in a phase 2a double-blind, randomized (3:1) trial of monthly VRs containing 25 mg DPV or placebo used continuously for 12 weeks. We assessed safety by adverse events (AEs). DPV concentrations were quantified in plasma and vaginal fluid. Steady-state concentrations were analyzed at 4, 8, and 12 weeks using repeated measures ANOVA. We assessed acceptability by self-report.
We found no differences in the proportion of women with related grade 2 or higher reproductive system AEs (DPV: 6/72 (8%), placebo: 3/24 (13%), P = .68) or grade 3 or higher AEs (DPV: 4/72 (6%), placebo: 0/24 (0%), P = .57). In the DPV arm, 2/72 (3%) declined to resume product use due to AEs. Median DPV concentrations in plasma (262.0 pg/mL at week 12) and vaginal fluid (40.6 ng/mg at week 12) were constant over 12 weeks and exceeded the in vitro 50% effective concentration by 5000-fold in vaginal fluid by week 4. VR acceptability was high; 84/93 (90%) "very much liked or liked" the VR.
DPV VRs were safe, well tolerated, and acceptable in postmenopausal women. Plasma concentrations were comparable to published data on DPV use in reproductive-age women (median plasma concentration: 264 pg/mL). Given the reassuring safety and pharmacokinetic data, the DPV VR is promising for preexposure prophylaxis in postmenopausal women.
NCT02010593.
绝经后女性具有独特的社会生物学人类免疫缺陷病毒（HIV）风险。我们评估了每月使用含有 25 毫克地匹福韦（DPV）的阴道环（VR）与安慰剂治疗绝经后女性的安全性、药代动力学和可接受性。
我们招募了 96 名 HIV 阴性的绝经后美国女性，参与一项为期 12 周的 2a 期双盲、随机（3:1）试验，每月使用含有 25 毫克 DPV 的 VR 或安慰剂连续使用。通过不良事件（AE）评估安全性。通过定量检测血浆和阴道液中的 DPV 浓度。采用重复测量方差分析评估第 4、8 和 12 周时的稳态浓度。通过自我报告评估可接受性。
我们发现，生殖系统相关 2 级或更高级别的 AE 发生率（DPV：72 例中有 6 例（8%），安慰剂：24 例中有 3 例（13%），P =.68）或 3 级或更高级别的 AE 发生率（DPV：72 例中有 4 例（6%），安慰剂：24 例中有 0 例（0%），P =.57）在两组之间没有差异。在 DPV 组中，有 2 例（3%）因 AE 而拒绝继续使用产品。第 12 周时，血浆中 DPV 的中位数浓度（262.0 pg/mL）和阴道液中的浓度（40.6 ng/mg）在 12 周内保持不变，第 4 周时阴道液中的浓度超过体外 50%有效浓度 5000 倍。VR 的可接受性很高；93 例中有 84 例（90%）“非常喜欢或喜欢”VR。
DPV VR 在绝经后女性中是安全的，耐受性良好且可接受。血浆浓度与生殖年龄女性中 DPV 使用的已发表数据相似（血浆浓度中位数：264 pg/mL）。鉴于令人放心的安全性和药代动力学数据，DPV VR 有望成为绝经后女性的暴露前预防方法。
NCT02010593。
