title: Efficacy, stability, and biosafety of sifuvirtide gel as a microbicide candidate against HIV-1.
abstract: Sifuvirtide is a proven effective HIV-1 entry inhibitor and its safety profile has been established for systemic administration. The present study evaluated the potential of sifuvirtide formulated in a universal gel for topical use as a microbicide candidate for preventing sexual transmission of HIV. Our data showed that sifuvirtide formulated in HEC gel is effective against HIV-1 B, C subtypes, CRF07_BC and CRF01_AE, the latter two recombinants represents the most prevalent strains in China. In addition, we demonstrated that sifuvirtide in gel is stable for at least 8 weeks even at 40°C, and did not cause the disruption of integrity of mucosal epithelial surface, or the up-regulation of inflammatory cytokines both in vitro or in vivo. These results suggest that sifuvirtide gel is an effective, safe and stable product, and should be further tested as a vaginal or rectal microbicide in pre-clinical model or clinical trial for preventing HIV sexual transmission.
authors.affiliation: Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Liangzhu
authors.initials: L
authors.lastname: Li
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Ben
authors.forename: Songhua
authors.initials: S
authors.lastname: Yuan
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
authors.forename: Jianqing
authors.initials: J
authors.lastname: Xu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D018938:Caco-2 Cells; D002482:Cellulose / Q000031:analogs & derivatives; D004355:Drug Stability; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005782:Gels / Q000494:pharmacology; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D051379:Mice; D009092:Mucous Membrane / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D015854:Up-Regulation; D014621:Vagina / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D005782:Gels; D010455:Peptides; C505768:sifuvirtide; D002482:Cellulose; C002283:hydroxyethylcellulose