Highly synergistic drug combination prevents vaginal HIV infection in humanized mice
Highly synergistic drug combination prevents vaginal HIV infection in humanized mice
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DOI：
10.1038/s41598-020-69937-5
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发表时间：
2020-08-03
影响因子：
4.6
通讯作者：
Gallay, Philippe A.
中科院分区：
文献类型：
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作者：
Baum, Marc M.;Ramirez, Christina M.;Gallay, Philippe A.
艾滋病毒-1疫情仍然是一个紧迫的全球卫生问题。年轻女性感染该病毒的风险更大。因此，需要一系列高效的、女性控制的、离散的阴道产品来帮助遏制疫情。口服富马酸替诺福韦(TDF)和恩曲他滨(FTC)在HIV-1暴露前预防(PrEP)中有效，并为阴道产品奠定了良好的基础。在这里，我们使用重复性很高的人源化小鼠模型，结合广谱中和抗体VRC01-N来评估TDF和FTC。这些药物分别和联合经阴道给药，并使用建立的严格的中效模型分析预防HIV-1的效果。令人惊讶的是，三重组合显示出高度的协同作用，对体内HIV-1PrEP来说是前所未有的，导致一些药物的剂量可能减少五倍。经阴道给药TDF-FTC-VRC01-N组合对HIV-1PrEP具有重要的前景。
The HIV-1 epidemic remains an urgent global health concern. Young women are disproportionately at risk of acquiring the virus. A range of highly effective, female-controlled, discrete vaginal products therefore is needed to help curb the epidemic. Oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) are effective in HIV-1 pre-exposure prophylaxis (PrEP) and form a promising basis for a vaginal product. Here, we evaluate TDF and FTC in combination with the broadly neutralizing antibody VRC01-N using a highly reproducible humanized mouse model. The agents were vaginally dosed individually and in combination, and the efficacy of HIV-1 prevention was analyzed using the established, rigorous median-effect model. Surprisingly, the triple combination showed a high degree of synergism, unprecedented for in vivo HIV-1 PrEP, leading to a possible fivefold dose reduction for some of the agents. Vaginal administration of the TDF-FTC-VRC01-N combination holds significant promise for HIV-1 PrEP.