Health Minister Barbara Hogan spoke to a gathering of leaders from all 53 African Red Cross and Red Crescent societies, saying new approaches were needed to help people with AIDS.
"They look upon us for a change in their plight. They look upon us for a renewal of their hope. We cannot fail, and we dare not fail them, for doing so we will be plunging our continent and its people into eternal pain and suffering," she said.
Her remarks were the latest high-profile speech to set a new tone for South Africa's approach to AIDS, in contrast with her widely derided predecessor, Manto Tshabalala-Msimang, known as "Dr Beetroot" for championing use of the vegetable to fight the disease.
Hogan took over the ministry in a political shake-up last month, in a move hailed by activists as an end to Tshabalala-Msimang's policies that for years questioned whether the HIV virus causes AIDS.
"In 2007, one in every three people in the world living with HIV lived in sub-Sahara Africa, a total of 22.5 million," Hogan said, warning that the dire statistics threatened to complicate efforts to tackle other problems, like climate change.
About 5.5 million people in South Africa have HIV, while four million children have been orphaned by the disease.