Scientists believe they are a step closer to understanding how to block HIV transmission between men and women.
HIV can enter and infect cells
A US and Swiss team used an experimental drug to protect monkeys from their equivalent of the virus.
It appeared to stop transmission across the vagina by binding with a cell surface molecule called CCR5 to prevent the virus infecting other cells.
The authors told journal Science their work was in its early stages and no such drug was yet available for humans.
Lead researcher Dr Michael Lederman, from the University Hospitals of Cleveland Centre for Aids Research, in Ohio, said: "We have identified a potential target that may offer a simple strategy for preventing HIV."
It is known that HIV can be transmitted between men and women at mucosal sites such as the vagina.
The virus uses certain cell surface molecules to get into cells and infect them.
One of these is called CCR5 and it had already been shown that people who lack this surface molecule on their cells are almost completely protected from acquiring HIV.
But HIV can use other target molecules to get into cells.
Dr Lederman's team set out to investigate whether blocking CCR5 would be enough to prevent simian HIV (SHIV) transmission.
They coated the vaginal surfaces of macaque monkeys with an experimental drug that would bind with CCR5, thereby making this surface molecule unavailable to SHIV.
The experimental drug, which is a modified version of a natural human protein called RANTES, protected the monkeys from SHIV infection.
Dr Lederman said: "There is still a lot of work to be done before we have an affordable, easy to use method of blocking transmission of HIV through the vaginal membranes.
"But we have taken an important step.
"Now that we have shown that it is possible to block SHIV transmission through the vagina in macaques and have identified the target molecule for blocking that transmission, the door is open to the development of a topical agent that could prevent infection with HIV in humans," he said.
Jo Robinson, from the Terrence Higgins Trust, said: "We welcome this important news which adds to existing information showing that it is possible to block HIV transmission in animal models.
"We urgently need new agents to be moved swiftly up the research process in order to ensure that products which are effective and safe to use in humans are made available as soon as possible.
"A microbicide could prevent millions of HIV infections over a short period of time if we are able to deliver it to those who need it most."
The findings of the US and Swiss team were presented at an American Medical Association meeting in Washington, the US.