HIV originally came from apes or monkeys, in which it is frequently a minor infection.
Prof Jonathan Ball, a virologist at the University of Nottingham, told the BBC: "If the trend continues then we might see the global picture change - a longer disease causing much less transmission.
"In theory, if we were to let HIV run its course then we would see a human population emerge that was more resistant to the virus than we collectively are today - HIV infection would eventually become almost harmless.
"Such events have probably happened throughout history, but we are talking very large timescales."
Prof Andrew Freedman, a reader in infectious diseases at Cardiff University, said this was an "intriguing study".
He said: "By comparing the epidemic in Botswana with that which occurred somewhat later in South Africa, the researchers were able to demonstrate that the effect of this evolution is for the virus to become less virulent, or weaker, over time.
"The widespread use of antiretroviral therapy may also have a similar effect and together, these effects may contribute to the ultimate control of the HIV epidemic."
But he cautioned HIV was "an awfully long way" from becoming harmless and "other events will supersede that including wider access to treatment and eventually the development of a cure".