Nel Annalene, Haazen Wouter, Nuttall Jeremy, Romano Joseph, Rosenberg Zeda, van Niekerk Neliëtte
aInternational Partnership for Microbicides, Silver Spring, Maryland, USA bSGS Life Science Services, Clinical Pharmacology Unit Antwerpen, Antwerp, Belgium cNWJ Group, LLC, Wayne, Pennsylvania, USA.
AIDS. 2014 Jun 19;28(10):1479-87. doi: 10.1097/QAD.0000000000000280.
Women-initiated HIV-prevention products are urgently needed. To address this need, a trial was conducted to assess the safety and pharmacokinetics of a silicone elastomer matrix vaginal ring containing 25 mg of the antiretroviral drug dapivirine when used continuously for 28 consecutive days.
A double-blind, randomized, placebo-controlled trial was conducted in 16 healthy, HIV-negative women, 18-40 years of age, who were randomized 1:1 to use either the active or matching placebo ring for 28 days. Participants were followed during and for 28 days after ring use for safety and pharmacokinetic evaluations.
The dapivirine vaginal ring was safe and well tolerated with no differences in safety endpoints between the active and placebo ring. The concentration-time plots of dapivirine in vaginal fluid were indicative of a sustained release of dapivirine over the 28 days of use. Dapivirine vaginal fluid concentrations were highest near the ring, followed by the cervix and introïtus (mean Cmax of 80, 67 and 31 μg/g, respectively). Vaginal fluid concentrations of dapivirine on the day of ring removal (day 28) at all three collection sites exceeded by more than 3900-fold the IC99 for dapivirine in a tissue explant infection model. Plasma dapivirine concentrations were low (< 1 ng/ml) and remained well below those observed at the maximum tolerated dose for oral treatment (mean Cmax of 2286 ng/ml).
The dapivirine vaginal ring has a safety and pharmacokinetic profile that supports its use as a sustained-release topical microbicide for HIV-1 prevention in women.
迫切需要由女性自主使用的艾滋病预防产品。为满足这一需求，开展了一项试验，以评估连续28天使用含25毫克抗逆转录病毒药物达匹韦林的硅橡胶弹性体基质阴道环的安全性和药代动力学。
对16名年龄在18至40岁之间、健康且未感染艾滋病毒的女性进行了一项双盲、随机、安慰剂对照试验，她们被1:1随机分配，使用活性阴道环或匹配的安慰剂阴道环28天。在使用阴道环期间及使用后28天对参与者进行随访，以进行安全性和药代动力学评估。
达匹韦林阴道环安全且耐受性良好，活性环和安慰剂环在安全性终点方面无差异。达匹韦林在阴道液中的浓度-时间曲线表明，在使用的28天内达匹韦林持续释放。达匹韦林在阴道液中的浓度在靠近阴道环处最高，其次是宫颈和阴道口（平均Cmax分别为80、67和31μg/g）。在所有三个采集部位，取出阴道环当天（第28天）的阴道液中达匹韦林浓度比组织外植体感染模型中达匹韦林的IC99高出3900倍以上。血浆中达匹韦林浓度较低（<1 ng/ml），且远低于口服治疗最大耐受剂量时观察到的浓度（平均Cmax为2286 ng/ml）。
达匹韦林阴道环的安全性和药代动力学特征支持其作为一种用于预防女性感染HIV-1的缓释局部杀菌剂使用。
