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New roadblock to HIV infection

The goal of developing an effective vaginal microbicide against HIV infection has eluded researchers ever since the first potential compound assessed, nonoxynol-9, proved to actually increase infection rates. In the Proceedings of the National Academy of Sciences, researchers led by Philippe Gallay at The Scripps Research Institute reported that syndecan-3, expressed on dendritic cells, presents a previously unknown route for HIV infection in vaginal mucosa. This finding may provide a strategy for developing another generation of microbicides that more completely address the process of HIV infection.

Development of microbicides has been slow in part because of a lack of validated animal models, markers for activity or true placebos. But development has also been slow because of the complex but incomplete picture of exactly how HIV infects vaginal mucosal cells.

First-generation microbicides did not specifically target HIV or HIV-host cell interactions, but instead took a broad-brush approach. Nonoxynol-9, the first such compound tested in clinical trials, caused inflammation that made vaginal mucosal cells more susceptible to HIV infection.

Second-generation microbicides, some of which are still in development, typically have been broad-spectrum, nonirritating polymers that were not specifically designed to target HIV but instead generically blocked the virus from interacting with host cells. But the lack of specificity has meant that most of these microbicides were likely to have limited effectiveness.

A few third-generation microbicides, some of which also remain in development, have taken a more focused approach by targeting the life cycle of the virus with non-nucleotide reverse transcriptase inhibitors (NNRTIs) or by targeting gp120 on the HIV envelope or the HIV co-receptor CC chemokine receptor 5

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