Anti-HIV gel trial fails
First anti-HIV microbicide to make it to the end of a clinical trial proves ineffective.
Carraguard, the first anti-HIV microbicide to make it to the end of phase III clinical trials has failed to prevent transmission of HIV.
The seaweed-derived vaginal gel microbicide was tested in 6,202 women in South Africa. Half the women were given Carraguard gel, and the other half received a placebo gel. They were all also given given condoms. Over the course of the trial, the researchers recorded 134 new infections in the Carraguard group and 151 in the placebo group, but the difference was not statistically significant.
“The results are the results. The gel doesn’t work,” says Alana de Kock, principal investigator for the portion of the trial run from the University of Cape Town. The trial was organised and run by the Population Council, a non-profit reproductive-health research organization based in New York.
The results add to the round of bad news associated with microbicide gels, of which five have recently entered clinical trials. Two of those trials have been stopped prematurely. The trial of a compound called cellulose sulphate, run by CONRAD, a reproductive health organization based in Arlington, Virginia, was stopped last year after early results indicated a slight increase in the chance of infection in the group using the gel. And the trial of a compound called C31G was stopped early in 2004 because the incidence of HIV in the test community was too low for a trial to be able to detect any effect of the treatment.
Two trials remain, both with different active ingredients: PRO 2000, developed by Indevus Pharmaceuticals in Lexington, Massachusetts; and BufferGel, under development by ReProtect in Baltimore, Maryland. One part of the PRO 2000 trial has also been stopped, after initial work suggested it would not have a significant effect.
Carraguard, based on the natural compound carrgeenan, showed promising results in early lab-based and animal-based trials. “Based on the basic science in the lab it was a very, very positive product,” says de Kock. But, she adds, “those are very controlled environments”.
Working with humans, especially in the area of sexual health, offers many more challenges. “The bottom line is it hasn’t worked in real women, in the real world,” she says.
Despite the failure of the trial, the Population Council was commended by the South African health minister for the care taken of the women on the trial. de Kock says it is important that the trial ran to completion, and showed that Carraguard was safe for long-term use. “It’s important to prove you can do a trial successfully in a community,” she says.
The scientists from the Population Council are now working on a combined product (PC815), which contains both Carraguard and an antiretroviral. The antiretroviral drug, called MIV-150, was shown to be ineffective as an oral drug because it was poorly absorbed by the body. But this property is useful in a vaginal gel as it keeps the drug on the surface and at the point of possible infection, says Melissa May, a spokesperson for the Population Council. This product is now in early safety trials with people.
It is still worth pursuing microbicides as an HIV preventative, says Sheena McCormack, from the UK’s Medical Research Council, who is involved in the PRO2000 trial. Even though the Carraguard trial could not show a statistical significance, the data show that the microbicide had a small effect. “It’s a signal in the right direction,” says McCormack. “As a scientist I’m very encouraged by that.”
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