Professors Salim Abdool Karim and Quarraisha Abdool Karim received the award from the Institute for Human Virology (IHV) in Baltimore in the US.
The award was presented to them by Robert Gallo, who discovered HIV as the cause of AIDS, at the 19th international meeting of the IHV.
"To me, both these renowned individuals have made some of the greatest contributions in the history of HIV/Aids in public health and epidemiology relevant to prevention and care of infected people," Gallo said in a statement.
"I don't know any person or persons who have done more to advance the proper care of people with HIV infection or the prevention of HIV infection among a population," Mr Gallo said.
Salim Abdool Karim is the director of the Centre for the Aids Programme of Research in South Africa (CAPRISA) and Professor Quarraisha Abdool Karim is its associate scientific director.
The researchers, who are currently involved in the development of innovative ways of preventing HIV in women, are both professors of epidemiology at Columbia University in New York and are honorary academics at the University of KwaZulu- Natal in South Africa.
They were the first to demonstrate that Antiretrovirals could prevent sexual transmission of HIV in 2010 when they shared the results of the CAPRISA 004 Tenofovir Gel trial.
The landmark study was recognised as one of the top 10 scientific breakthroughs of the year.
The couple discovered that the Tenofovir Gel prevents
Genital Herpes. It was the first drug proven to be effective against this disease.
"We accept the award not just on our own behalf, but in recognition of the resilience and contributions of the thousands of South Africans, who have been central, as participants in the research, to the ongoing effort to develop better and more effective HIV prevention and treatment strategies," Salim Abdool Karim said.
Quarraisha, one of the most highly-respected infectious disease epidemiologists in South Africa, said she "deeply appreciated" the award from a centre of excellence in HIV research like the IHV.
AIDS (acquired immunodeficiency syndrome) is a syndrome caused by a virus called HIV (human immunodeficiency virus). The disease alters the immune system, making people much more vulnerable to infections and diseases.