A pill used to treat people with HIV can also prevent infection by the Aids virus, a landmark study has found.
Scientists found that daily doses of the combination drug Truvada cut the risk of gay and bisexual men catching HIV by almost 73%.
Experts said the findings marked a turning point in the worldwide war against HIV and Aids.
However, they pointed out that the study focused on just one high risk group, "men who have sex with men".
More research was needed to see if the approach worked for other populations such as injecting drug users and vulnerable women.
The iPrEx (pre-exposure initiative) study was the first to assess the effectiveness of using an anti-retroviral drug to guard against HIV infection.
A total of 2,499 participants from the US, Peru, Ecuador, Brazil, South Africa, and Thailand, were randomly assigned to take Truvada on a daily basis or an inactive "dummy" placebo pill.
The men were also provided with condoms and counselling.
After an average 14 months, there were 36 new HIV infections among the treated group and 64 among men given the placebo.
The researchers, led by Dr Robert Grant, from the University of California at San Francisco, calculated that taking Truvada reduced the overall risk of HIV infection by around 44%.
But many of the men failed to take the pill every day. Among those who took the drug more than 90% of the time, there were nearly 73% fewer infections. Study participants who were compliant with the treatment, according to blood tests, had a 90% lower risk of HIV infection than those who were not.
The findings were published online today in the New England Journal of Medicine.
Commenting on the results, Jim Pickett, from the Aids Foundation of Chicago, said: "This discovery alters the HIV prevention landscape forever.
"While this level of efficacy is relatively strong, PrEP (pre-exposure prophylaxis) is not quite ready for prime time and work remains before this strategy is rolled out. However, we are thrilled to have a new prevention option beyond male and female condoms visible on the horizon."
His words were echoed by Mitchell Warren, head of the Aids Vaccine Advocacy Coalition, a US non-profit organisation that works on HIV prevention, who said: "This is a great day in the fight against Aids, a major milestone."
Another US expert, Professor Sharon Hillier, head of reproductive infectious disease research at the University of Pittsburgh School of Medicine, said: "iPrEX has proved the concept of oral PrEP and now it's up to the field to build on this success and work toward realising the full potential of this promising approach in different at-risk populations, such as injection drug users and women in places like sub-Saharan Africa.
"None of us can do this alone, but collectively I am convinced that we can, and that there will be the day when we have several safe and effective methods for preventing HIV."
Dr Kevin Fenton, Aids prevention chief at the US Centers for Disease Control and Prevention, called the results a "major advance" but warned that a pill should "never be seen as a first line of defence against HIV".
"It's not time for gay and bisexual men to throw out their condoms," he said.
More than 40 million people around the world are HIV positive and 7,500 new infections occur each day.
Truvada is a pill made from a combination of two retroviral drugs, tenofovir and emtricitabine. Normally it is given to people already infected with HIV to prevent the virus replicating and hold back its spread.
Cost may restrict use of the pill as a preventative measure. The medicine costs between 5,000 US dollars (£3,142) and 14,000 dollars (£8,797) a year in the US, according to the AP news agency, but only 39 cents (20p) per day in poor countries where it is sold in a generic form.
The research was welcomed by both the Joint United Nations Programme on HIV/AIDS (Unaids) and the World Health Organisation (WHO).
Michel Sidibe, Unaids executive director, said: "This positive result is going to give hope to millions of men who have sex with men and help them protect themselves and their loved ones."
WHO director general Dr Margaret Chan said: "The trial opens exciting new prospects. It shows that oral pre-exposure prophylaxis can reduce the risk of HIV infection in men who have sex with men.
"We look forward to further examining these data to consider how we can best use this tool to enhance HIV prevention when used in combination with other prevention such as condom promotion in this population at higher risk."
Results from the Caprisa trial earlier this year showed that a vaginal microbiocide gel containing tenofovir could reduce HIV infections in women by 39%.