Long-distance drivers and sex workers who operate along a busy route from Abidjan to Lagos are being targeted in a new project funded by the World Bank.
Travellers infected by HIV-positive sex workers can spread the disease
Education and services designed to stop the spread of HIV and Aids will be established along the transport corridor which is used by up to three million people a year.
The World Bank approved a $16.6m grant to fund the project on Thursday, marking the first time it has backed a cross-border HIV/Aids initiative in Africa.
"HIV doesn't respect borders, it exploits borders," said Keith Hansen, World Bank manager for the Aids Campaign Team for Africa.
Popular international routes such as the Abidjan-Lagos corridor which crosses five countries can become real sources of trouble, he explained.
Whereas individual countries might run HIV/Aids awareness programmes and while people might take precautions in their home areas, the situation can become very different once they go on the road.
Customs and attitudes may be different or there may just be more temptations - such as drivers wanting to find something to do while they wait maybe days for customs clearance, Mr Hansen said.
Stopping 'next catastrophe'
The west African nations involved in the new project have lower rates of HIV prevalence than some southern African nations, with between 3% and 9.7% of adults estimated to be HIV-positive, according to the World Bank.
But sex workers are far more likely to be infected, with rates as high as 85.4% in Cotonou in Benin and 74% in Accra, Ghana's capital city, the organisation says.
While Bank officials hope that the corridor will help to stop the spread of the epidemic in less affected countries, they say similar projects could be introduced almost anywhere.
"We have one catastrophe in Africa," Mr Hansen said, referring to the devastation Aids has wreaked in countries like Botswana and South Africa where observers say a generation of people has been lost to the disease.
"One of our goals is to stop the mortgaging of the future of the next generation. A very large majority of Africans are HIV-negative and we would look to keep it that way."
The World Bank funding may be used for, among other things, education, providing condoms or setting up health services along the transport corridor, depending on what the interest and needs are.
Much of the grant will be given to local groups and aid agencies and many people may not know of the World Bank's involvement as it may seem that projects are developed by their unions or other organisations.
The new $16.6m grant was approved at a board meeting at the World Bank headquarters in Washington.
It comes under a broader project known as the Multi-Country HIV/Aids Programme for Africa which has provided $1bn so far which the World Bank says makes it the leading financial supporter of such projects in the continent.
The corridor action may last a few years, but Mr Hansen says it will be impossible to get any evidence that the epidemic is being turned around in such a short time.
But there is confidence that it will be a success and similar projects are already being considered for other areas.