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University of Minnesota
March 4, 2009
Ashley Haase and Pat Schlievert have discovered a compound that may help control the spread of HIV.
Glycerol monolaurate blocked vaginal infection of the nonhuman primate version of HIV
By Nick Hanson
Researchers at the University of Minnesota have identified a compound that, applied vaginally, can prevent transmission of the primate version of HIV, called SIV.
While it's not a cure and the compound still must go through human clinical trials before it used to prevent HIV, the research is a step toward preventing the devastating disease that affects 33 million people around the globe.
Ashley Haase and Pat Schlievert, principal and co-investigator, respectively, in the Department of Microbiology, researched glycerol monolaurate (GML), a naturally occurring compound the FDA recognizes as safe. It is widely used as an anti-microbial and anti-inflammatory agent in food and cosmetics.
"After 25 years, an effective vaccine for HIV is still on the distant horizon, so not only vaccines, but all research into ways to prevent the continued spread of this lethal virus, remain critically important," Haase says. "If GML as a topical microbicide can add to our prevention, it could contribute to saving millions of lives."
After sexual exposure to SIV, the researchers found that the primates' natural defense system is activated, rushing immune cells (T-cells) to the scene of the infection. The virus uses these T-cells as fuel to expand infection locally and spread it throughout the body.
"So even though it sounds counter-intuitive, halting the body's natural defense system might actually prevent transmission and rapid spread of the infection," Haase says. "That's where GML comes in."
"After 25 years, an effective vaccine for HIV is still on the distant horizon, so not only vaccines, but all research into ways to prevent the continued spread of this lethal virus, remain critically important."
They examined GML because in 1992 Schlievert began using it to combat toxic shock syndrome, a potentially lethal bacterial infection. In recent years, research has shown GML is active against a variety of toxins and microbes and inhibits cytokines and chemokines, small molecules that play key roles in triggering the body's defense system.
Since it is the defense system they wanted to inhibit, it made sense to see if GML might prevent transmission, Haase says.
Before testing their theory, the researchers tested GML's safety by daily vaginal application of a GML gel-based topical solution and a neutral solution as a control. They found no adverse effects of GML in the monkeys.
"GML is recognized as safe, and is already approved for acute human use, but we were now able to show that GML could be safely applied every day for months," Schlievert says.
The researchers applied GML to five monkeys; five other monkeys were left untreated as a control group. An hour after GML application, the two groups of monkeys were injected with an infectious dose of the virus.that in a tissue culture will infect 50 percent of the cells. Four hours later, the monkeys were again treated with GML and then given a second dose.
The researchers monitored the animals for evidence of transmission for two weeks, after which time infected animals would typically have hundreds of millions of virus particles circulating in the bloodstream. If there was no evidence of infection, the treatments and viral challenges were repeated. Four of five of the control group contracted SIV, while none of the five GML-treated group showed any evidence of acute infection after receiving as many as four large doses of virus.
The research is published in the March 4, 2009, online edition of Nature.
The researchers believe GML has potential to effectively prevent transmission of HIV to women, which is how a majority of new cases are acquired around the globe. Of the more than 33 million people infected with HIV or diagnosed with AIDS, 67 percent live in the sub-Saharan region of Africa, and women represent close to 60 percent of new infections in this center of the pandemic.
But Haase cautions that much work remains to be done before planning clinical trials in humans, including additional testing in other animals and developing dosing and delivery methods that will make it more likely that women will use GML to prevent HIV. Longer-term follow-up studies are also needed into occult, or hidden, infections that weren't apparent in the acute stage of infection but manifest months later.
"GML is exceptionally inexpensive, is widely used in foods and cosmetics, and is easy to formulate in many ways for vaginal use," Schlievert says. "The compound has been demonstrated in vitro to inhibit the growth of nearly all sexually transmitted disease microorganisms, and other causes of vaginal infections, without affecting normal bacteria. Its use by women may significantly improve overall vaginal health."
The National Institutes of Health funded the research. Collaborators include the University of Minnesota Medical School, School of Public Health, and College of Pharmacy; the Wisconsin National Primate Research Center at the University of Wisconsin-Madison; and the SAIC Frederick, Inc., at the National Cancer Institute in Frederick, Md.