An intravaginal ring that releases the NNRTI MIV-150 reduces SHIV transmission in macaques

释放 NNRTI MIV-150 的阴道环可减少猕猴的 SHIV 传播

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作者:Rachel Singer #, Paul Mawson #, Nina Derby #, Aixa Rodriguez, Larisa Kizima, Radhika Menon, Daniel Goldman, Jessica Kenney, Meropi Aravantinou, Samantha Seidor, Agegnehu Gettie, James Blanchard, Michael Piatak Jr, Jeffrey D Lifson, José A Fernández-Romero, Melissa Robbiani, Thomas M Zydowsky

Abstract

Microbicides may prevent HIV and sexually transmitted infections (STIs) in women; however, determining the optimal means of delivery of active pharmaceutical ingredients remains a major challenge. We previously demonstrated that a vaginal gel containing the non-nucleoside reverse transcriptase inhibitor MIV-150 partially protected macaques from SHIV-RT (simian/HIV reverse transcriptase) infection, and the addition of zinc acetate rendered the gel significantly protective. We test the activity of MIV-150 without the addition of zinc acetate when delivered from either ethylene vinyl acetate (EVA) or silicone intravaginal rings (IVRs). MIV-150 was successfully delivered, because it was detected in vaginal fluids and tissues by radioimmunoassay in pharmacokinetic studies. Moreover, EVA IVRs significantly protected macaques from SHIV-RT infection. Our results demonstrate that MIV-150-containing IVRs have the potential to prevent HIV infection and highlight the possible use of IVRs for delivering drugs that block HIV and other STIs.

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