Microbicides: AIDS dream is dealt a new blow
2007-02-01

Category AIDS Drugs Contraceptive Vaccines Nations South Africa Switzerland Uganda Nigeria India City Geneva Category AIDS Infectious Diseases

One of the most important quests in AIDS research -- a gel that women could use to prevent HIV infection during intercourse -- has suffered its second major setback in little more than six years.

Bereft of a cure or vaccine against a disease that has claimed more than 25 million lives in as a quarter century, scientists are doggedly pursuing the path of vaginal microbicides. These are creams that a woman would apply, rather like contraceptive spermicides today, to block or kill the AIDS virus.

To the dismay of the tight-knit community of microbicide scientists, two out of six advanced trials of candidate gels have been stopped for safety reasons, providing a reminder of the many unknowns and risks that hedge their work.

Researchers testing cellulose sulphate found that women who used the gel ran a higher risk of HIV infection compared with those who used a dummy lookalike, or placebo. As a precaution, another trial using this compound was stopped.

Zeda Rosenberg, head of the International Partnership for Microbicides (IPM), the vanguard of the microbicide offensive, said the outcome, announced by UNAIDS and the World Health Organisation (WHO) on Thursday, was "a profound disappointment."

"The closure of these trials is a stark reminder that drug development in general is a difficult and unpredictable process, and we must constantly bear in mind that the majority of drugs that enter the clinical trial process fail," said Rosenberg.

The cellulose sulphate, also called Ushercell, was in Phase III trials, the final and biggest step in testing a pharmaceutical innovation for safety and effectiveness.

The trial had been conducted in South Africa, India, Uganda and the West African country of Benin, said Tim Farley, of WHO's Department of Reproductive Health and Research in Geneva.

A similar trial involving cellulose sulphate was stopped in Nigeria as a precaution, although there was no data to suggest that there was any risk.

Cellulose sulphate is based on an HIV-blocking sticky molecule derived from cotton.

Three other microbicides are also in Phase III trial and use a different molecule but the same blocking method, called HIV entry inhibition.

They comprise Carraguard, in Phase III, which is being tested in South Africa, whose results are expected by the end of the year; and PRO2000 and BufferGel, being tested in three trials in eastern and southern Africa, whose results are due in 2008 and 2009.

An anti-HIV gel has been one of the most alluring dreams for AIDS campaigners.

It holds out the possibility of a cheap, easy-to-use shield, thus empowering women in sub-Saharan countries who may face coercive sex by an infected partner.

In 2000, tests of an over-the-counter spermicide, nonoxynol-9, found it amplified, not reduced, the risk of HIV infection. The apparent source: the gel caused vaginal lesions that made it easier for the virus to enter the bloodstream.

One problem facing microbicide trials is that volunteers may become lax about safe sex, in the belief that they are now protected.

Conrad, a not-for-profit US health organisation that was carrying out the Ushercell research where the infections occurred, said it was investigating the failure.

The compound had passed 11 safety trials involving more than 500 people, and the women in the Phase III trial had been closely briefed about HIV prevention and were given high-quality condoms free of charge.

Conrad added that, before the trial, it had set aside funds to provide treatment and HIV drugs to any women who became HIV-positive during the test.

At the International AIDS Conference in Toronto last August, microbicides were held up as one of the greatest areas of promise.

The research has been enthusiastically adopted by Bill and Melinda Gates, who declared it an "immediate priority" for their philanthropy. Microbicide funding in 1997 was 28 million dollars; in 2005, it was 163 million.

The International AIDS Society, the world's biggest independent association of HIV/AIDS professionals, said it was extremely disappointed at the new setback.

But, it vowed, precious knowledge would be coaxed from the failure.

"This will strengthen future microbicide research and increase our overall knowledge of how such compounds work," said IAS President Pedro Cahn.