NAIROBI, Sept 23 (AFP) - An HIV-killing barrier cream, used like a spermicidal contraceptive gel, is one of the most important yet also most elusive goals in the fight against AIDS, a top scientist said here Tuesday.
Given that an HIV vaccine "is certainly many years away," the quest is on to find a microbicide to provide protection during intercourse, said Mark Wainberg, director of McGill University's AIDS Centre in Montreal, Canada.
The right formula would deliver a body blow to AIDS, especially in Africa, where women are often coerced by their partners into having unprotected sex, he told the biggest conference on the African AIDS crisis.
The ideal microbicide would not require further metabolism, such as a chemical, to make it work; it would be stable inside and outside the vaginal cavity; and it would not require refrigeration, he said.
But the hunt for it has been hampered by scientific setbacks, by the wily shape-changing nature of the human immunodeficiency virus (HIV), and by a chronic lack of interest from Big Pharma, he said.
Initially, scientists cast around for a microbicide that worked in "a non-specific way" against HIV -- tough compounds that not only destroyed HIV but other micro-organisms as well.
"Unfortunately, these approaches seem to have failed," Wainberg said.
Indeed, the first product to be given a large trial, an over-the-counter spermicide gel called nonoxynol-9 tested among 765 female sex workers in Benin, Ivory Coast, South Africa and Thailand, was a catastrophic failure.
It not only failed to prevent HIV infection, it actually seemed to boost the risk of becoming infected.
Among women who used the gel frequently --- at least three and a half applications a day -- the risk of infection was nearly twice as high as among volunteers who used a lookalike placebo.
The speculated reason for this is that the gel damaged the delicate mucal lining of the vagina, opening the way to viral penetration of the bloodstream.
That disappointment has shifted attention towards harnessing drugs, called non-nucleoside reverse transcriptase inhibitors (NNRTIs), which are well known weapons in the AIDS pharmaceutical arsenal.
NNRTIs latch on to a specific enzyme on the virus surface, preventing the virus from integrating its DNA with that of the immune cell.
Some of these, notably compounds called PMPA, UC781 and Calanolide A, have performed well in various tests using tissue cultures, macaque monkeys and mice that have been genetically modified to replicate the symptoms of AIDS.
Other possibilities are using these drugs with other compounds to attack multiple targets on the virus, such as a molecule like T-20, which blocks the virus before it attaches to a cell.
But there is still a long way to go before any of the candidate treatments gets out of the lab and into human trials, a three-phase process of testing for safety and effectiveness that can take years.
And even so, many uncertainties remain. Some microbicides may not ward of new, resistant forms of the fast-mutating virus.
And instead of acting as a barrier in the vaginal or anal wall, some microbicides could be absorbed into the bloodstream -- not enough to kill the virus, but enough to encourage it to mutate into a resistant form.
Wainberg said the frustrations of finding a microbicide almost exactly mirrored those of the search for an HIV vaccine.
Part of the problem, he said, was "we have not done a very good job in involving the major pharmaceutical companies of the world," which had little interesting in pursuing research for a product, sold in poor countries, that would yield little profit.
Just as in vaccines, a way had to be found by governments and agencies to provide a profit incentive for research, and leave it to donations to bring down the cost for poor countries when the product finally reaches the market, he said.
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