US researchers have found that a compound widely used as an anti-microbial and anti-inflammatory agent effectively blocked infection of the non-human primate version of HIV in monkeys; a step that is being heralded as a breakthrough in developing a version that works in humans to help prevent a devastating disease that affects about 33 million people around the world.
The discovery is published as an advanced access online paper in the 4 March issue of Nature and was the work of Drs Ashley Haase and Pat Schlievert, principal and co-investigator, respectively, in the Department of Microbiology at the University of Minnesota, and colleagues.
Haase, Schlievert and colleagues discovered that a compound called glycerol monolaurate (GML) applied as a vaginal gel stopped transmission of the nonhuman primate version of HIV, known as SIV.
It is not a cure and the drug still has to undergo trials to prove it is safe and effective in humans. The US Food and Drug Administration recognize it is safe and has approved it as an anti-microbial and anti-inflammatory agent in food and cosmetics.
Haase said in a press statement that:
“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.”
“If GML as a topical microbicide can add to our prevention, it could contribute to saving millions of lives,” said Haase.
Haase, Schlievert and colleagues applied GML as a vaginal gel to five monkeys and they also had five other monkeys as controls that were not treated with GML.
An hour later they injected the treated and untreated monkeys with an infectious dose of SIV, and four hours after that the treatment group received the GML gel again and both groups had a second dose of the virus.
The monkeys were monitored for a further two weeks: the normal progression of the virus once an animal in infected is that two weeks later, the bloodstream would contain hundreds of millions of virus particles. Monkeys showing no evidence of infection were treated again at the two week mark: the treatment group with GML and viral doses, and the control group just with the viral doses.
After receiving four large doses of the virus, none of the GML treated group showed any evidence of acute infection while five of the control group had contracted SIV.
The researchers think that sexual exposure to SIV causes the monkey’s immune system to rush T-cells to the scene and this is the advantage that SIV seeks. Like its human equivalent HIV, SIV uses the T-cells as fuel to help itself replicate locally and then spread to the rest of the body.
Halting this natural immune response could be the key to preventing transmission and rapid spread, and “that’s where GML comes in,” said Haase.
They decided to try GML because in 1992 Schlievert began using it to treat toxic shock syndrome, a potentially lethal bacterial infection, and more recent studies have shown that it works against a number of toxins and microbes and it also blocks cytokines and chemokines, molecules that help to trigger immune responses.
So they decided to try GML as a way to stop SIV/HIV transmission since it appeared to be an effective way to hold back the immune response that the virus relied on for survival.
The researchers think GML has potential as a vaginal gel to prevent HIV transmission to women, which is the route the virus now takes for most of the new cases arising throughout the world.
Haase said there was still a lot of work to be done before GML can safely and effectively be used to prevent HIV infection in women, including more animal testing, and testing dosing and delivery methods that make it easy for women to use. Longer term studies will also be needed to check for other infections that don’t show themselves until months afterwards.
Schlievert said GML is cheap and widely used in foods and cosmetics and it would not be difficult to formulate it for vaginal use.
“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,” he added.
The National Institutes of Health paid for the study.
“Glycerol monolaurate prevents mucosal SIV transmission.”
Qingsheng Li, Jacob D. Estes, Patrick M. Schlievert, Lijie Duan, Amanda J. Brosnahan, Peter J. Southern, Cavan S. Reilly, Marnie L. Peterson, Nancy Schultz-Darken, Kevin G. Brunner, Karla R. Nephew, Stefan Pambuccian, Jeffrey D. Lifson, John V. Carlis & Ashley T. Haase.
Nature, advance online publication 4 March 2009.
doi:10.1038/nature07831
Sources: Journal abstract, University of Minnesota News.
Written by: Catharine Paddock, PhD