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HIV treatment begins to gel

October 30, 2005 By Narelle Towie This article courtesy of Nature News.

Microbicide promises much in the battle against AIDS.

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A triple-action gel has been shown to restrict the spread of an HIV-related virus in monkeys, raising hopes for a fresh weapon in the fight against AIDS.

Yet to be tested in humans, the gel would be applied to the vagina before sex and could afford women discreet protection against HIV. It has the potential to slow the spread of AIDS and save millions of lives.

The treatment is being developed by drug companies Bristol-Myers Squibb, based in New York, and Merck, headquartered in Whitehouse Station, New Jersey. It combines three compounds, each of which has a different way of preventing the virus from infecting the body's cells, and is thought to be more potent than any treatments currently being tested.

The three-pronged approach is similar to the idea of using a combination of antiviral medicines to treat HIV-positive patients, notes Jim Turpin, a microbiologist at the US National Institutes of Health in Bethesda, Maryland.

Solid results

Researchers at Tulane National Primate Research Center in Covington, Louisiana, tested the three components, both separately and in combination in various gels, in a group of 51 female macaques.

After applying a gel, they gave the monkeys a high dose of simian-human immunodeficiency virus (SHIV), a hybrid version of HIV and SIV that closely resembles the human strain.

On average, 75% of monkeys given just one of the inhibitors were protected, whereas the three monkeys that received the combination gel escaped infection in all cases. The results are published online by Nature today1.

Single file

No anti-HIV microbicide has so far been approved for widespread human use, but five single-action gels are undergoing clinical trials in Africa. These studies are not due to end until 2007.

Trials of these compounds have shown modest success in monkeys, says Sharon Hillier, who studies sexually transmitted diseases at the University of Pittsburgh in Philadelphia. But previous monkey trials have used a strain of HIV that infects cells in a different way to the one that causes the sexually transmitted infection in humans, meaning that the results may not be directly comparable.

Only one microbicide trial has been completed in humans, with disastrous results (see ' Starting to gel'). The women involved in a trial for nonoxynol-9 became more susceptible to HIV because the gel, which was essentially a detergent, damaged their vaginal tissue. The same compound is used as a spermicidal coating for condoms, but higher doses are needed to combat HIV. "It turned toxic at the same concentration as it killed the virus," says Hillier.

Combined force

The triple-action gel takes a different approach. It uses compounds that block the virus's entry into host cells by targeting a range of different proteins, rather than attempting to wipe the virus out completely. This means that there is no need to use detergents that cause vaginal inflammation, say the researchers, led by John Moore of Cornell University in New York.

The combination gel could also potentially be applied several hours before sex: in the macaque study, the triple gel was still 50% effective 6 hours after application. Gels currently undergoing human tests have to be applied immediately before sex.

This will make the triple-action gel easier to use in real-life situations, says Charlotte Watts, a health-policy expert at the London School of Hygiene and Tropical Medicine. Using a treatment that can be applied in advance may help the many women, particularly in the developing world, whose partners disapprove of condoms and similar measures.

In the end, Watts says, the more approaches that are available the better. "We need to move towards a range of products that suits everyone." But with the average cost of bringing a new treatment to market standing at tens of millions of dollars, progress is slow-going, she adds.

References

  1. Veazey R. S., et al. Nature, 438. 99 - 102 (2005).

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