The frustrating quest to develop a vaginal gel to prevent HIV infection was dealt a fresh blow on Monday as researchers announced that the first prototype to complete advanced clinical trials was ineffective.
Carraguard, a candidate microbicide produced by the Population Council that had spent three years in large-scale 'Phase 3' trials, was unable to prevent transmission of the AIDS virus, the investigators said.
But the gel was found to be safe for long-term vaginal use, a finding they described as extremely promising.
'This is the first phase 3 microbicide efficacy trial to be completed with no safety concerns,' said prinicipal investigator Khatija Ahmed. '(...) However, the study was unable to show Carraguard's efficacy in preventing male-to-female transmission of HIV.'
The trial ran from March 2004 to March 2007 at three sites in South Africa among 6,262 women.
Half of the volunteers were given the Carraguard gel and condoms, while the other half were given a placebo gel and condoms. All were given HIV education and safer-sex counselling.
In the Carraguard group, 134 new HIV infections occurred, slightly fewer than the 151 in the placebo group. But Ahmed said the difference was not statistically significant and did not constitute evidence that Carraguard was effective.
It is the third major setback in the seven-year-long drive to develop a vaginal microbicide, the term for a cream that would block or kill the AIDS virus during vaginal intercourse.
Microbicides are one of the most eagerly-sought avenues in the war on AIDS, where at present there is neither a cure nor a vaccine and prevention depends on the condom or abstinence.
Scientists are grappling for a means by which women, who are physically more at risk from AIDS infection than men, can protect themselves without having to rely on male consent to wear a condom.
In February 2007, trials of a cellulose sulphate called Ushercell were stopped ahead of schedule after women who used the gel were found to run a higher risk of HIV infection compared with those who used a dummy lookalike, or placebo.
Cellulose sulphate is based on an HIV-blocking sticky molecule derived from cotton.
Carraguard uses the same blocking method, called HIV entry inhibition, but is a different molecule.
In the same category as Carraguard are PRO2000 and BufferGel, being tested in three trials in eastern and southern Africa, whose results are due in 2008 and 2009 respectively.
However, last week the PRO2000 trial was scaled down, as it was found that the higher-strength formulation of the cream was found to be ineffective. A lower-strength formulation is still being tested.
In 2000, tests of an over-the-counter spermicide, nonoxynol-9, found it amplified, not reduced, the risk of HIV infection. The gel apparently caused vaginal lesions that made it easier for the virus to enter the bloodstream.
Ahmed said the encouraging safety results of Carraguard would allow it to be used as a vehicle for future products, such as a gel that would incorporate an anti-retroviral drug to kill the AIDS virus.
An estimated 33.2 million people, in a range from 30.6 to 36.1 million, are living with AIDS or the human immunodeficiency virus (HIV) that causes it, the specialised UN agency UNAIDS says.
South Africa has become a key testing ground for strategies against the global AIDS pandemic. It has 5.5 million people with HIV or AIDS, the highest number of any country in the world.