The new gel would be a huge benefit to African women bearing the brunt of the AIDS pandemic.
A vaginal gel used before and after intercourse could significantly decrease the chances of HIV infection.
Further tests are needed to validate the results and test the safety and effectiveness of the gel.
Twenty-five million people have died from AIDS and more than 33 million others today are infected by HIV.
Scientists on Monday reported a major stride towards a vaginal gel that can thwart HIV, a goal that would be a huge benefit to African women bearing the brunt of the AIDS pandemic.
A prototype cream tested in South Africa reduced the risk of infection by the human immunodeficiency virus (HIV) by 39 percent overall, but by 54 percent among those women who used it most consistently, they said.
The study coincided with the six-day 18th International AIDS Conference, which opened in Vienna on Sunday.
The results must now be validated in a third, wider phase in the arduous process of assessing a new medication for safety and effectiveness.
Although several questions have yet to be answered, the findings are a bright ray of hope in the 29-year campaign against acquired immunodeficiency syndrome (AIDS), the researchers said.
"Without this gel, we may see 10 women becoming infected in a year. With this gel, we would see only six women becoming infected," said Salim Abdool Karim, one of the two leading co-researchers, in a teleconference with reporters.
Twenty-five million people have died from AIDS and more than 33 million others today are infected by HIV, which causes the disease.
More than two-thirds of these live in sub-Saharan Africa, where 60 percent of new infections occur among women and girls.
One of the big vectors of transmission is through coercive intercourse by an infected partner who is unwilling to wear a condom.
The gel that was tested contains a one-percent formulation of tenofovir. It is a frontline component in the "cocktail" of antiretroviral drugs that disrupt HIV reproduction in immune cells.
Previous microbicides that have been tested have not contained an antiretroviral, and have had either a very low level of protection or even boosted the risk of infection.
Over nearly three years, the gel was tested among 445 HIV-negative women, while 444 counterparts received a harmless lookalike called a placebo.
They were then tested for HIV at monthly follow-up visits, where they were also given counselling in safe sex, access to condoms and treatment for sexually-transmitted disease.
Each participant was asked to insert, using a vaginal applicator, a first dose of the gel within 12 hours before sex followed by a second dose as soon as possible but within 12 hours afterwards, said co-leader Quarraisha Abdool Karim, also of the Centre for the AIDS Programme of Research in South Africa (CAPRISA) in Durban..
Compared to the placebo group, the gel reduced the risk of HIV infection by 39 percent overall, but by 54 percent among women who adhered to the instructions most faithfully.
There was no increase in side effects, nor -- among women who became infected with HIV -- any sign that they were more resistant to tenofovir as a result of the gel.
Despite this good news, the scientists said they still had to tackle several important issues.
One is why the gel seemed to be less effective after about 18 months.
This may be due to weakened adherence to the cream, they suggested. About 40 percent of the women in the trial used the microbicide less than one time out of two.
The trial was conducted in an urban setting (Durban) and a rural setting (Pietermaritzburg) KwaZulu-Natal province, enrolling sexually active women aged 18 to 40 considered to be of high risk of exposure to HIV.
It was a so-called IIb trial, meaning that it had passed earlier scrutiny for safety and effectiveness, but was still relatively small compared to a Phase III test involving several thousand volunteers.
The study, published by the journal, Science, was to be the focus of a seminar on Wednesday at the world AIDS forum.
If -- eventually -- the gel is approved for use, it will join a small but growing arsenal of preventative tools against HIV.
For a long time, the condom was the only method that had a confirmed high degree of protection from HIV in intercourse.
Four years ago, it was joined by male circumcision. Removal of the foreskin, which contains cells that are vulnerable to penetration by HIV, can reduce HIV risk by more than half, but only for men and not for women.
Availability of a microbicide that is 60 percent effective would avert two and a half million infections over three years, according to a 2003 mathematical study.