Hopes of a breakthrough that would allow women to protect themselves from HIV have been dashed with today's revelation from a large, British-funded trial that a promising microbicide has turned out to be ineffective.

Britain's Medical Research Council (MRC) and the department for international development (DfID) had backed the trial in four African countries, involving 9,385 women. But after four years and significant investment, scientists have been forced to conclude that the PRO 2000 gel does not prevent HIV/Aids.

Dr Sheena McCormack of the MRC, chief investigator of the trial known as MDP 301, said they were deeply disappointed, but that the search must go on.

A microbicide, in the form of a vaginal cream or gel that kills the virus, would give women in Africa and Asia the power to defend themselves against HIV given the refusal of many men to wear condoms. The trials in Africa showed that both men and women found its use acceptable.

Expectations were raised in March when a smaller US-led trial of PRO 2000, involving 3,099 women, found a 30% reduction in infections, but the actual numbers of people who became HIV positive were not large enough to give conclusive results.

"I have to say then we got quite excited," said McCormack. "But in a big trial you get closer to the truth, and unfortunately the truth is it didn't work. It is bitterly disappointing for us, but it will inform the way we go forward."

Half the participants were given PRO 2000 while the other half got an inactive gel. There were 130 infections among those who used the real thing and 123 among those who had the placebo.

The hunt for a microbicide was given a big boost when Clare Short, as international development secretary, enthusiastically endorsed it in 2002 as a gender and equity issue. Her department gave £14m to the MRC, Imperial College and five African countries. The final cost to DfID of the PRO 2000 trial has been £40m, with £2m from the MRC – a substantial sum, but tiny compared with the cost of pharmaceutical company trials.

Other gains were made, however, despite the results. Professor Gita Ramjee, who enrolled 2,385 women at her centre in Durban, South Africa, said they had received health checks and treatment for conditions from high blood pressure to potential cervical cancer that would not otherwise have been picked up. All the women and their partners had also been counselled on avoiding HIV and given condoms.

But Ramjee, who has conducted five separate microbicide trials, said she felt "very despondent" at having to tell her staff and the participants that the gel did not work. "A lot of my staff are HIV positive and do a lot of counselling and they hear the pleas of women who say we desperately need something to prevent HIV infection because our partners don't want to wear condoms," she said.

About 2.7 million people were infected with HIV last year. A number of African countries have run out of money to put newly diagnosed people on drugs to keep them alive and will struggle to continue to treat those already taking them if donations fall because of the economic crisis. There is a danger, said McCormack, that it is "going to go wrong again for Africa".

If PRO 2000 had worked, it could have been made available cheaply over the counter to any woman who wanted it.

Scientists have turned their attention to the possibility of adapting anti-retroviral drugs given to stop HIV becoming Aids. One of the possibilities is a gel form of Tenofovir, a drug that could also be taken daily in tablet form to prevent HIV infection. But such gels or tablets would have to be given out through clinics with supervision, and there are fears that the virus could become resistant to them.