Tenofovir Douche as HIV Preexposure Prophylaxis for Receptive Anal Intercourse: Safety, Acceptability, Pharmacokinetics, and Pharmacodynamics (DREAM 01)

作者：Ethel D. Weld, Ian McGowan, Peter A. Anton, Edward J. Fuchs, Ken Ho, Alex Carballo‐Diéguez, Lisa C. Rohan, Rebecca Giguere, Rhonda M. Brand, Stacey Edick, Rahul P. Bakshi, Teresa L. Parsons, Madhuri Manohar, Aaron Seigel, Jared Engstrom, Julie Elliott, Cindy Jacobson, Christina Bagia, Lin Wang, Amer Al‐khouja, Douglas J. Hartman, Namandjé N. Bumpus, Hans Spiegel, Mark A. Marzinke, Craig W. Hendrix · 发表于：The Journal of Infectious Diseases · 年份：2023 · DOI：10.1093/infdis/jiad535 · 被引用次数：17 · 研究领域：HIV/AIDS Research and Interventions、HIV/AIDS drug development and treatment、HIV Research and Treatment

BACKGROUND: Despite highly effective HIV preexposure prophylaxis (PrEP) options, no options provide on-demand, nonsystemic, behaviorally congruent PrEP that many desire. A tenofovir-medicated rectal douche before receptive anal intercourse may provide this option. METHODS: Three tenofovir rectal douches-220 mg iso-osmolar product A, 660 mg iso-osmolar product B, and 660 mg hypo-osmolar product C-were studied in 21 HIV-negative men who have sex with men. We sampled blood and colorectal tissue to assess safety, acceptability, pharmacokinetics, and pharmacodynamics. RESULTS: The douches had high acceptability without toxicity. Median plasma tenofovir peak concentrations for all products were several-fold below trough concentrations associated with oral tenofovir disoproxil fumarate (TDF). Median colon tissue mucosal mononuclear cell (MMC) tenofovir-diphosphate concentrations exceeded target concentrations from 1 hour through 3 to 7 days after dosing. For 6-7 days after a single product C dose, MMC tenofovir-diphosphate exceeded concentrations expected with steady-state oral TDF 300 mg on-demand 2-1-1 dosing. Compared to predrug baseline, HIV replication after ex vivo colon tissue HIV challenge demonstrated a concentration-response relationship with 1.9 log10 maximal effect. CONCLUSIONS: All 3 tenofovir douches achieved tissue tenofovir-diphosphate concentrations and colorectal antiviral effect exceeding oral TDF and with lower systemic tenofovir. Tenofovir douches may provide a ...