Highly synergistic drug combination prevents vaginal HIV infection in humanized mice.

Abstract

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.

• Authors: Marc M Baum, Christina M Ramirez, John A Moss, Manjula Gunawardana, Michael Bobardt, Philippe A Gallay
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 12995 (08 03 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 32747682 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antiviral Agents
• Drug Combinations
• Tenofovir
• Emtricitabine

Topics

• Administration, Intravaginal
• Animals
• Antiviral Agents (administration & dosage)
• Drug Combinations
• Drug Synergism
• Emtricitabine (administration & dosage)
• Female
• HIV Infections (prevention & control)
• Humans
• Mice
• Tenofovir (administration & dosage)
• Vagina