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Twenty-eight years after AIDS was first recognized, preventing the transmission of HIV remains an elusive goal. Clinical trials of strategies aimed at preventing transmission to women, including virus-inhibiting compounds called microbicides, have been disappointing. On page 1034, microbiologist Ashley Haase at the University of Minnesota in Minneapolis and his colleagues show that microbicides may yet prove beneficial. While investigating the earliest stages of simian immunodeficiency virus (SIV) infection in rhesus macaques, the team revealed how this HIV-like virus exploits the host's normal immune response in order to fuel systemic spread. This led them to test a seemingly unorthodox strategy — blocking the host's immune response with microbicides to deprive the virus of the cells it uses to spread. Haase tells Nature more.

How did your work lead to testing a microbicide in this unusual way?

Despite the large dose of virus used to infect animals, we discovered that founder populations of infected cells are small and focal. We were puzzled by how these barely detectable populations could so quickly turn into an explosive systemic infection. By detailed mapping of infected cell clusters in cervical tissues, we established that the clusters grow by accreting newly infected cells. We then pieced together how the virus takes advantage of the host's inflammatory response to infection to recruit new target cells for its spread. The response brings in circulating T cells, HIV's target cells, and in so doing provides an opportunity for the virus to spread systemically.

Were you surprised that an existing antimicrobial compound was effective?

Yes. My co-author Patrick Schlievert has been working with glycerol monolaurate (GML) for 17 years. He previously showed that it blocks the signalling and immune-response system we wanted to disrupt, so we thought it might be effective as a microbicide. And it was. Four out of five animals challenged with repeated high doses of SIV were completely protected from infection by GML therapy.

Have your data met with excitement or scepticism?

Both. Many people are as excited as we are about GML's potential, but there is also scepticism about it being another microbicide that does not specifically target HIV. But we have advanced the idea that blocking the host's inflammatory immune response might prevent vaginal transmission. Ultimately, I think combining microbicides with specific antiretroviral compounds might be the most effective way to prevent infection.