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Several recent medical studies have reported circumcision cuts the risk of HIV infection among men by 50-60 percent, and the findings have been backed by UNAIDS.
"These (African) countries should now prepare how to introduce circumcision on a large scale," UNAIDS chief Dr. Peter Piot told Reuters. "The science is clear."
Baby boys should be targeted first but then attention should switch to adolescent boys and adult men, said Piot, who is in New Delhi to meet Indian officials on how they plan to tackle the world's largest HIV/AIDS caseload.
In 2005, UNAIDS said that more research was needed into the possible benefits of circumcision before it could be promoted as part of national HIV programs.
One U.S.-Ugandan study found male circumcision also reduces infections in female partners by 30 percent.
Muslim and Jewish men have to be circumcised according to religious beliefs, and Piot said that UNAIDS understood advocating mass circumcision was a religiously and culturally sensitive issue for many people.
"Changing that is touching very much on the core of values. That is going to make it more complicated than any other medical issue that I can think of."
But he said given the grim HIV situation in southern Africa, it was important to promote the idea of widespread circumcision.
"We are faced with an absolute crisis where you have 20-40 percent of adults being HIV-positive ... you need to use every scientifically proven method to bring down the new infections."
South Africa, Botswana and Nambia are among the worst hit countries in the region, while Swaziland has an infection rate of around 50 percent, UNAIDS says.
Piot said that even if large-scale circumcision was introduced, countries should continue to promote condom use as well as abstinence.