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• W4328125138 abstract "Abstract Adolescent girls and young women in low- to middle-income countries are disproportionately at risk of becoming HIV-1 infected. New non-vaccine biomedical products aimed at overcoming this global health challenge need to provide a range of safe, effective, and discreet dosage forms based on the delivery of one or more antiviral compounds. An overarching strategy involves vaginal drug administration through inserts/tablets, gels, films, and intravaginal rings. The approach derives its appeal from being women-controlled and topical, there-by potentially minimizing systemic exposure to the agents and their metabolites. Oral regimens based on tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) are established and effective in HIV-1 pre-exposure prophylaxis (PrEP), and form a promising basis for vaginal PrEP. Here, we used bone marrow/liver/thymus humanized mice to measure the in vivo efficacy against HIV-1 of single and combination antiviral compounds applied vaginally, coupled with data analysis using the Chou-Talalay mathematical model to study the dose–effect characteristics. Unexpectedly, strong antagonism was observed in drug combinations composed of TDF-FTC coupled with a third agent using a different mode of action against HIV-1. The antagonistic effect was remedied when TDF was omitted from the regimen. Our approach provides a translational template for the preclinical, rational, and systematic evaluation of drug combinations for the prevention of HIV-1, and other viral diseases." @default.
• W4328125138 created "2023-03-22" @default.
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• W4328125138 date "2023-03-21" @default.
• W4328125138 modified "2023-09-25" @default.
• W4328125138 title "Acute antagonism in three-drug combinations for vaginal HIV prevention in humanized mice" @default.
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• W4328125138 doi "https://doi.org/10.1038/s41598-023-31695-5" @default.
• W4328125138 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36944714" @default.
• W4328125138 hasPublicationYear "2023" @default.
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