The Microbicide Trials Network-017 study was undertaken to characterize the safety, acceptability, pharmacokinetic (PK), and pharmacodynamic profile of the reduced-glycerin (RG) 1% tenofovir (RG-TFV) gel compared to oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF). The study was a Phase 2, three-period, randomized sequence, open-label, expanded safety and acceptability crossover study. In each 8-week study period, HIV-1-uninfected participants were randomized to RG-TFV rectal gel daily or RG-TFV rectal gel before and after receptive anal intercourse (RAI) (or at least twice weekly in the event of no RAI), or daily oral FTC/TDF. A mucosal substudy was conducted at sites in the United States and Thailand. Samples were collected to evaluate PK and ex vivo biopsy challenge with HIV-1. A total of 195 men who have sex with men and transgender women were enrolled in the parent study and 37 in the mucosal substudy. As previously reported, both products were found to be safe and acceptable. Systemic TFV concentrations were significantly higher following oral exposure and daily rectal administration compared to RAI-associated product use (p < .001). All three routes of pre-exposure prophylaxis (PrEP) administration resulted in the inhibition of explant infection (p < .05), and there was a significant inverse correlation between explant HIV-1 p24 and tissue concentrations of TFV and FTC (p < .0001). Despite significant differences in systemic and mucosal drug concentrations, all three PrEP regimens were able to protect rectal explants from ex vivo HIV infection. These data suggest that there is a rationale for co-development of oral and topical antiretroviral PrEP for HIV prevention.

中文翻译：

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替诺福韦凝胶和口服恩曲他滨/富马酸替诺福韦地索普西的开放标签药代动力学和药效学评估

Microbicide Trials Network-017 研究旨在描述与口服恩曲他滨/富马酸替诺福韦二吡呋酯相比，减少甘油 (RG) 1% 替诺福韦 (RG-TFV) 凝胶的安全性、可接受性、药代动力学 (PK) 和药效学特征（联邦贸易委员会/贸易发展基金）。该研究是一项 2 期、三期、随机序列、开放标签、扩展安全性和可接受性交叉研究。在每个 8 周的研究期间，未感染 HIV-1 的参与者在接受肛交 (RAI) 之前和之后（或在没有 RAI 的情况下至少每周两次）每天随机分配到 RG-TFV 直肠凝胶或 RG-TFV 直肠凝胶), 或每日口服 FTC/TDF。在美国和泰国的地点进行了一项粘膜子研究。收集样品以评估 PK 和离体HIV-1 的活检挑战。共有 195 名男男性行为者和变性女性参加了父母研究，37 名参加了粘膜亚组研究。正如之前报道的那样，这两种产品都被发现是安全且可接受的。与 RAI 相关产品使用相比，口服暴露和每日直肠给药后全身 TFV 浓度显着更高 ( p  < .001)。所有三种暴露前预防 (PrEP) 给药途径都抑制了外植体感染 ( p  < .05)，外植体 HIV-1 p24 与组织中 TFV 和 FTC 浓度呈显着负相关 ( p <.0001)。尽管全身和粘膜药物浓度存在显着差异，但所有三种 PrEP 方案都能够保护直肠外植体免受体外HIV 感染。这些数据表明，有理由共同开发用于预防 HIV 的口服和局部抗逆转录病毒 PrEP。