Department of Chemistry, Oak Crest Institute of Science, 128-132 W. Chestnut Ave., Monrovia, CA, USA.
Los Angeles (UCLA) Fielding School of Public Health, University of California, 650 Charles E. Young Dr. South, 16-035 Center for Health Sciences, Los Angeles, CA, USA.
Sci Rep. 2020 Aug 3;10(1):12995. doi: 10.1038/s41598-020-69937-5.
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.
HIV-1 疫情仍然是全球紧急关注的健康问题。年轻女性面临不成比例的感染病毒的风险。因此，需要一系列高效、女性控制、离散的阴道产品来帮助遏制疫情。口服替诺福韦酯二异丙醇富马酸（TDF）和恩曲他滨（FTC）在 HIV-1 暴露前预防（PrEP）中有效，并为阴道产品提供了有前途的基础。在这里，我们使用高度可重现的人源化小鼠模型评估 TDF 和 FTC 与广泛中和抗体 VRC01-N 的组合。单独和联合阴道给予这些药物，并使用既定的严格中位数效应模型分析 HIV-1 预防的效果。令人惊讶的是，三联组合显示出高度的协同作用，这是体内 HIV-1 PrEP 前所未有的，导致一些药物的剂量可能减少五倍。TDF-FTC-VRC01-N 联合阴道给药为 HIV-1 PrEP 提供了很大的希望。
