A new microbicide has proved successful in preventing infection with the AIDS virus in monkeys. The compound holds promise for developing barriers to HIV in humans.
Most big pharmaceutical companies involved with AIDS have focused on antiretroviral drugs or vaccines, not microbicides. Recently nonprofits and governments have significantly increased their investments in developing microbicidal gels or creams that could be applied to the vagina or rectum to prevent infection. One strategy is to block HIV's ability to infect its favorite target.
HIV typically enters the body by passing through mucosal cells that line the vagina and rectum and homing in on white blood cells that circulate underneath. The virus establishes a foothold by attaching to so-called CD4 receptors on the white blood cells and then grabbing a second receptor known as CCR5.
Clinical immunologist Michael Lederman of Case Western Reserve University in Cleveland, Ohio, teamed up with Oliver Hartley of the University of Geneva in Switzerland, whose lab had created a CCR5 inhibitor, PSC-RANTES. Working with a group led by pathologist Ronald Veazey of the Tulane National Primate Research Center in Covington, Louisiana, they applied different doses of the compound to the vaginas of 30 monkeys. Fifteen minutes later, they administered an intravaginal dose of a chimeric monkey/human AIDS virus. In animals given relatively high doses of PSC-RANTES, 12 of 15 completely resisted infection, they report in the 15 October issue of Science.
"This experiment suggests that blocking CCR5 alone is enough to prevent infection," says Lederman. Researchers had wondered whether it would be necessary to cut off all the virus' routes of entry to prevent infection, not just the CD4/CCR5 nexus. Although the dose of PSC-RANTES required for protection in this study is "too high to be practical," Lederman says, the study also used a large dose of virus, suggesting that smaller amounts of the compound might work in the real world.
"This is the first paper that says if you target the susceptible cells, you can block [mucosal] infection," says virologist Robin Shattuck of St. George's Hospital Medical School in London. "We've moved from an era of trying unsophisticated approaches to rational drugs that we understand," Shattuck says.