Ex vivo comparison of microbicide efficacies for preventing HIV-1 genomic integration in intraepithelial vaginal cells.

Antimicrobial Agents and Chemotherapy
M Juliana McElrathFlorian Hladik

Abstract

Vaginally applied microbicides hold promise as a strategy to prevent sexual HIV transmission. Several nonspecific microbicides, including the polyanion cellulose sulfate, have been evaluated in large-scale clinical trials but have failed to show significant efficacy. These findings have prompted a renewed search for preclinical testing systems that can predict negative outcomes of microbicide trials. Moreover, the pipeline of potential topical microbicides has been expanded to include antiretroviral agents, such as reverse transcriptase, fusion, and integrase inhibitors. Using a novel ex vivo model of vaginal HIV-1 infection, we compared the prophylactic potentials of two forms of the fusion inhibitor T-20, the CCR5 antagonist TAK-778, the integrase inhibitor 118-D-24, and cellulose sulfate (Ushercell). The T-20 peptide with free N- and C-terminal amino acids was the most efficacious compound, causing significantly greater inhibition of viral genomic integration in intraepithelial vaginal leukocytes, measured by an optimized real-time PCR assay, than the more water-soluble N-acetylated T-20 peptide (Fuzeon) (50% inhibitory concentration [IC50], 0.153 microM versus 51.2 microM [0.687 ng/ml versus 230 ng/ml]; P<0.0001). In contra...Continue Reading

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Citations

Oct 7, 2011·Journal of Virology·Lamar BallweberFlorian Hladik
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Dec 12, 2012·Current HIV/AIDS Reports·Charlene S Dezzutti, Florian Hladik
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Aug 29, 2021·Viruses·Germán Gustavo GornalusseFlorian Hladik

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