Results of the South African study are being presented at the International AIDS Conference in Vienna and were published online Monday by the journal Science.
"It's the first time we've ever seen any microbicide give a positive result that you could say was statistically significant," said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.
The gel, spiked with the AIDS drug tenofovir, cut the risk of HIV infection by 50 percent after one year of use and 39 percent after 2 1/2 years, compared to a gel that contained no medicine.
In the study, women used the gel only 60 percent of the time; those who used it more often had higher rates of protection, and researchers said this is the key to improving effectiveness, not changing the gel.
The gel also cut in half the chances of getting HSV-2, the herpes virus that causes genital warts.
Even partial protection is a huge victory that could be a boon not just in poor countries but for couples anywhere when one partner has the AIDS virus and the other does not, said Dr. Salim Abdool Karim, the South African researcher who led the study. In the U.S., nearly a third of new infections each year are among heterosexuals, he noted.
The gel is in limited supply; it was made for this and another ongoing study from a drug donated by California-based Gilead Sciences Inc., which sells tenofovir in pill form as Viread.
The study tested it in 889 heterosexual women in and near Durban, South Africa. Half were given the microbicide and the others, a dummy gel. Women were told to use it 12 hours before sex and as soon as possible within 12 hours afterward.
At the study's end, there were 38 HIV infections among the microbicide group versus 60 in the others.
The gel seemed safe -- only mild diarrhea was slightly more common among those using it. Surveys showed that the vast majority of women found it easy to use and said their partners didn't mind it. And 99 percent of the women said they would use the gel if they knew for sure that it prevented HIV.