Scientists identify compound that could prevent HIV transmission

Scientists at the University of Minnesota have identified a compound that, applied vaginally, can prevent transmission of the primate version of HIV, called SIV. The study is published in the 4 March 2009 online edition of Nature. Ashley Haase, M.D., head of the University of Minnesota Department of Microbiology, principal investigator of the study, and Pat Schlievert, Ph.D., professor in the Department of Microbiology, and-co-investigator, researched Glycerol Monolaurate (GML), a naturally occurring compound that the FDA recognises as safe. It is widely used as an antimicrobial 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 remains critically important,' Haase said. '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 body's natural defence 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 defence system might actually prevent transmission and rapid spread of the infection,' Haase said. 'That's where GML comes in.'

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 defence system. Since these were the processes they wanted to inhibit, it made sense to see if GML might prevent transmission, Haase said.

Before testing their theory, the researchers tested GML's safety by daily vaginal application of two types of a GML gel-based topical solution. A group of nine monkeys received warming gel with GML added; the other group of three monkeys received warming gel alone as a control.

'GML is recognised 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 said.

The researchers then challenged five GML-treated and five control animals with large doses of the SIV - an infectious dose that in a tissue culture will infect 50 percent of the cells - to see if GML could prevent transmission and infection.

An hour after applying GML the two groups of monkeys were injected with this large dose of the virus. 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 - infected animals would typically have hundreds of millions of viruses circulating in the blood stream. 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.

Researchers believe GML has potential to be an effective way to prevent vaginal transmission of HIV in humans, 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 epicentre of the pandemic.

But Haase added that there is still a lot of work to be done before planning clinical trials in humans, including additional testing in animals and developing a dosing and a delivery method that will make it more likely that women will use GML to prevent HIV, and longer term follow up studies into occult infections that weren't apparent in the acute stage of infection, but are 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 said. '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 research was funded by the National Institutes of Health. Collaborators include the University of Minnesota Medical School, School of Public Health and College of Pharmacy, the Wisconsin Primate Research Centre, and the National Cancer Institute.