The researchers found that most of the macaques pre-treated with rectal tenofovir gel up to 2 hours before the viral challenge were partly or totally protected from SIV infection.
Animals that were untreated or treated with a placebo gel became infected with SIV.
Some of the protected macaques were also found to developed T-cell immune responses to the virus.
The researchers say that their findings suggest that topical treatment with antiretroviral drugs before exposure might be used to prevent rectal HIV transmission in people.
They, however, concede that efficacy cannot be shown conclusively in animal studies.
They also revealed that human trials of a potential vaginal microbicide that worked well in macaques were halted recently because women using the microbicide showed increased rates of HIV infection.
Given that HIV targets activated T cells, the researchers are of the opinion that experiments should be conducted to check that the observed immune responses do not increase the likelihood of infection on later exposure before this approach can be tested in humans.
The study has been published in the journal PLoS Medicine.