Microbicide Gel Fails to Protect

The field of microbicide research was dealt a blow this month when a gel known as PRO 2000, which had shown some promise in an earlier study, failed to have any effect in preventing HIV infection in a Phase III efficacy trial involving 9,385 women in the UK, Tanzania, South Africa, Zambia, and Uganda.

At the conclusion of the MDP 301 trial, which lasted four years, 130 HIV infections had occurred among women who received PRO 2000, compared to 123 infections among those who received an inactive placebo gel. This analysis excluded HIV-infected women who became pregnant during the trial, as well as women whose HIV infections were detected within a year after their first study visit. Another analysis that included all HIV infections, regardless of pregnancy or time of infection, was equally disappointing: 145 HIV infections in the microbicide group compared to 143 in the placebo group.

PRO 2000 is a topical gel that women apply before intercourse. It is composed of a synthetic compound that was non-specifically designed to block attachment of HIV to host cells and thereby prevent infection. Women in the MDP 301 trial were also given condoms and regular HIV prevention counseling. The trial was conducted by the Microbicide Development Programme, a partnership of 16 African and European research institutions, and was primarily funded by the UK’s Medical Research Council.

A year ago, researchers reported results from a smaller Phase IIb study of 3,099 women in South Africa, Malawi, Zambia, Zimbabwe, and the US, which showed that women who received PRO 2000 gel along with condoms had 30% fewer HIV infections than those who received the placebo gel and condoms (see VAX February 2009 Spotlightarticle, Canvassing CROI). This finding, though promising, was not statistically significant.

HIV prevention advocates expressed disappointment at the results of MDP 301, but said the field should continue to press forward in developing microbicides that are gel formulations of existing antiretrovirals (ARVs). “The need for a microbicide is as great as ever,” says Salim Abdool Karim, a clinical infectious disease specialist who led the Phase IIb trial of PRO 2000. “This should not be a time for despondency, we need to move on.” —Regina McEnery