Mayer Kenneth H, Maslankowski Lisa A, Gai Fang, El-Sadr Wafaa M, Justman Jessica, Kwiecien Antonia, Mâsse Benoît, Eshleman Susan H, Hendrix Craig, Morrow Kathleen, Rooney James F, Soto-Torres Lydia
Miriam Hospital/Brown University, Providence, Rhode Island 02906, USA.
AIDS. 2006 Feb 28;20(4):543-51. doi: 10.1097/01.aids.0000210608.70762.c3.
To establish the highest practical dose and frequency (HPDF) of 0.3% or 1% tenofovir vaginal gel applied once or twice daily by sexually abstinent HIV-uninfected women, and to evaluate the safety, tolerability and systemic pharmacokinetics of the HPDF in abstinent and sexually active HIV-negative and HIV-infected women.
Eighty-four women, enrolled in sequential cohorts, used the study product for 14 consecutive intermenstrual days. Safety laboratory assessments and pelvic examinations were carried out during five study visits, with colposcopy at enrollment and on day 14. Samples for pharmacokinetics were collected before and after the initial tenofovir gel use and at day 13.
The 1% tenofovir gel used twice daily was as well tolerated as other regimens used by the 48 HIV-negative sexually abstinent women, establishing the HPDF. Although 92% of the women reported at least one adverse event, the majority were mild (87%) and involved the genitourinary tract (70%). One possibly product-related severe adverse event involving lower abdominal cramping was reported by a sexually abstinent woman who used 0.3% gel twice daily. Serum tenofovir levels were low but detectable in 14 of the 25 women. No new HIV RNA resistance mutations were detected after 2 weeks of tenofovir gel in the 24 HIV-infected participants. No significant systemic toxicity was detected.
A 2-week course of 1% tenofovir vaginal gel used twice daily was well tolerated in sexually abstinent and sexually active HIV-negative and HIV-positive women. Systemic tenofovir absorption occurred. Expanded safety and effectiveness testing is warranted.
确定未感染HIV且禁欲的女性每日使用一次或两次0.3%或1%替诺福韦阴道凝胶的最高实际剂量和频率（HPDF），并评估该HPDF在禁欲及有性行为的HIV阴性和HIV感染女性中的安全性、耐受性及全身药代动力学。
84名女性按序贯队列入组，在连续两个月经周期的14天内使用研究产品。在五次研究访视期间进行安全性实验室评估和盆腔检查，入组时及第14天进行阴道镜检查。在首次使用替诺福韦凝胶之前和之后以及第13天采集药代动力学样本。
48名HIV阴性且禁欲的女性使用每日两次的1%替诺福韦凝胶，其耐受性与使用其他方案的女性相同，从而确定了HPDF。尽管92%的女性报告至少发生了一次不良事件，但大多数为轻度（87%），且涉及泌尿生殖道（70%）。一名每日使用两次0.3%凝胶的禁欲女性报告了一例可能与产品相关的严重不良事件，涉及下腹部绞痛。25名女性中有14名血清替诺福韦水平较低但可检测到。24名HIV感染参与者在使用替诺福韦凝胶2周后未检测到新的HIV RNA耐药突变。未检测到明显的全身毒性。
每日两次使用1%替诺福韦阴道凝胶，疗程为2周，在禁欲及有性行为的HIV阴性和HIV阳性女性中耐受性良好。发生了替诺福韦的全身吸收。有必要进行扩大的安全性和有效性测试。
