About 10,000 healthy African women are to test the effectiveness of a microbicide gel in protecting against HIV, in a major UK-funded study.
Sub-Saharan Africa has the highest HIV infection rates
The women, from South Africa, Tanzania, Zambia and Uganda, will apply the gel before sex, as well as using condoms.
The US-developed gel can block HIV's entry into human cells.
The four-year study forms part of a £42m programme funded by the Medical Research Council and the Department for International Development.
The gel, developed by US pharmaceutical company Indevus, has been shown to protect animals against infection.
PRO 2000, which is applied to the vagina, has also been found to be effective against other sexually-transmitted infections including chlamydia, herpes and gonorrhoea.
The women in the trial, which begins in Uganda and South Africa before expanding to other sites in South Africa, Tanzania and Zambia by the end of the year, will be split into three groups.
They will randomly be given either a dummy gel or PRO 2000 at one of two different strengths.
They will apply the gel before having sex but will also use condoms and be given sexual health counselling.
Anatoli Kamali, from the Medical Research Council (MRC) unit in Uganda, said the trials were being conducted in sub-Saharan Africa because that was where the highest HIV infection rates could be found.
MRC clinical trials manager Juli Bakobaki added: "Showing this microbicide protects against HIV would represent a tremendous breakthrough in the fight against the spread of HIV/Aids."
The Microbicides Development Programme will be co-ordinated by Imperial College London and the MRC Trials Unit, working with other groups in Africa and the UK.