Efficacy, stability, and biosafety of sifuvirtide gel as a microbicide candidate against HIV-1.

Efficacy, stability, and biosafety of sifuvirtide gel as a microbicide candidate against HIV-1.
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西夫韦肽凝胶作为 HIV-1 候选杀菌剂的功效、稳定性和生物安全性

DOI:
10.1371/journal.pone.0037381
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Zhang X
Zhang X
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li L;Ben Y;Yuan S;Jiang S;Xu J;Zhang X

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西夫韦肽是一种有效的HIV-1进入抑制剂,其安全性已被确定为全身给药。本研究评估了西夫韦肽作为预防艾滋病毒性传播的候选杀微生物剂的潜力。我们的数据显示西夫韦肽HEC凝胶制剂对HIV-1 B、C亚型、CRF 07_BC和CRF 01_AE有效,后两种重组体代表了中国最流行的毒株。此外,我们证明了凝胶中的西夫韦肽即使在40°C下也稳定至少8周,并且在体外或体内均不引起粘膜上皮表面完整性的破坏或炎性细胞因子的上调。提示西夫韦肽凝胶剂是一种有效、安全、稳定的产品,可作为阴道或直肠杀菌剂进行预防HIV性传播的临床前模型或临床试验。
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.
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