After a string of depressing trial results, the fourth international microbicides conference in New Delhi, India, kicked off this week with a ray of hope that new research could deliver a new generation of HIV prevention approaches for women.

It has been a disappointing year for scientists and activists. First, there was the early closure of clinical trials using a cellulose sulphate-based microbicide, after preliminary findings indicated higher HIV infections in the active group compared to the placebo group.

Then came last week's announcement from the US-based reproductive health organisation, Population Council, that Carraguard - the first microbicide to complete the advanced stage of clinical testing - had failed to prevent HIV infection.

Pamela Mthembu, of South Africa's Medical Research Council, has found all this gloom hard to take. She has been working to educate communities in KwaZulu-Natal about microbicides - the province hardest hit by the HIV/AIDS epidemic - and told IRIN/PlusNews that "delivering bad news" was the hardest part of her job.

The Carraguard setback had been particularly disappointing because there was "so much hope" pinned to the product, said Dr Salim Abdool-Karim, director of the Centre for the AIDS Programme of Research in South Africa (CAPRISA).

Microbicides are usually creams or gels applied inside the vagina or rectum to prevent sexually transmitted infections (STIs), including HIV; they have generated a high level of interest because they give women control over protection decisions.

But the latest reverse has raised the fear that donor and government support for microbicides could fade. However, Dr Sharon Hillier, a principal investigator with the US-based Microbicides Trials Network (MTN), warned that "it would be really naïve" to expect all the microbicide products tested so far to have been successful.

"We're not there yet. Only three ... [substances] have gone through [for testing: cellulose sulphate, Nonoxyl9 and Carraguard]. That's it ... we don't need to beat ourselves up so much," she told microbicide advocates at a workshop ahead of the conference. "Our failures should only renew our interest because we're in a place of great hope in HIV prevention research."

Are ARV-based microbicides the solution?

A new buzz has now been generated by the concept of microbicides based on antiretroviral (ARV) drugs, with researchers trying to discover whether ARVs - which prolong the lives of people who are HIV positive - might also prevent HIV infection if they are used as externally applied microbicides.

In the same way that the ARV drug, nevirapine, has been used as a prophylactic in mother-to-child transmission of the virus, researchers are hoping that adding an ARV compound to a cream or gel could create a microbicide that would prevent a woman exposed to HIV during sex from becoming infected.

On Monday, 25 February, MTN released the results of a phase-two study on the safety of a vaginal microbicide containing the ARV drug, tenofovir, which found that sexually active HIV-negative women could use the gel safely every day for an extended period of time. The women's adherence to the product was also high.

"Finding that daily use is both safe and feasible is important, because we believe a daily approach may provide more sustainable protection against the virus in women who can't always predict when they will have sex," said the MTN's Hillier.

Researchers from the CAPRISA centre in Durban, South Africa, are now investigating whether the tenofovir gel can protect women from HIV infection. In October 2008, MTN will embark on a larger study of tenofovir gel, involving over 4,000 women in Africa. They will also test whether taking ARV pills orally is an effective form of HIV prevention.

MTN's John Mellors acknowledged that using the same drugs to prevent HIV as are used to treat HIV was "not an optimal situation", but was the "most likely route to success".

One of the biggest concerns is drug resistance. CAPRISA's Abdool-Karim told IRIN/PlusNews that if a woman stayed negative while using an ARV-based microbicide, drug resistance was not an issue; but women who became positive while using the microbicide could develop resistance to treatment.

"It's a concern we take very, very seriously and it's going to require a huge effort in monitoring and measuring resistance, and other concerns," said Karim.