Preliminary tests suggest HIV infection can be treated using a disabled version of the virus itself.
HIV attacks immune cells
University of Pennsylvania researchers treated five patients, who had not responded to drugs, with disabled HIV.
It carried added genetic material that blocks HIV reproduction and as a result HIV levels in the patients' blood either stabilised or decreased.
The research raises the prospect that gene therapy might provide an alternative to antiretroviral drugs.
The long-term effectiveness of the drugs is under threat from the growing problem of drug resistance.
Researcher Dr Carl June said: "Gene therapy has long been discussed as an alternative treatment for HIV.
"The goal of this trial was safety and feasibility and the results established that.
"But the results also hint at something much more."
The patients selected for the trial had failed to respond to at least two antiretroviral regimens of drugs.
They were given a single infusion of their own immune system T cells that had been removed from their blood, purified and genetically modified to carry the manipulated version of HIV.
Each patient received around 10 billion T cells - between 2% and 10% of the total number in an average person.
The disabled HIV gene used by the researchers was modified to carry an antisense RNA molecule, which scrambles the process of reading genetic information and is designed to sabotage the process HIV uses to reproduce itself inside infected cells.
Genetic material is added to a disabled HIV sample
Viral loads of the patients remained stable or decreased during the nine month trial - and one subject showed a sustained dramatic decrease in viral load.
T-cell counts remained steady or increased in four of the five patients.
The researchers were able to detect the modified cells in patients for months, and in some cases years after the infusion.
However, they warn that the trial was very small, and said patients would be monitored for 15 years to assess long-term effects.
Dr Bruce Levine, who also worked on the study - published online in Proceedings of the National Academy of Science - said: "Just because this has produced encouraging results in one or two patients doesn't mean it will work for everyone. We have much more work to do."
Dr George Schmid, a specialist in HIV at the World Health Organization, said it could take many years to determine whether the technique was safe and effective, but he said the results were "encouraging".
Roger Pebody, of the charity Terrence Higgins Trust, said: "Gene therapy is complex and would be a totally different strategy for HIV treatment.
"Although in its early stages, this research seems to indicate that this approach may be safe and the results are hopeful."
Edwin Bernard, editor of the journal Aids Treatment Update, said gene therapy was likely to be a labour-intensive, expensive treatment designed for individuals, and so not available to the vast majority of people with HIV/Aids who live in developing countries.
He said new drug treatments currently under development might provide an alternative.
It is hoped the approach could be adapted to tackle other diseases.
The researchers believe the use of viruses like HIV, lentiviruses, may prove particularly effective in gene therapy.
Lentiviruses are especially effective at infecting T cells, and also infect non-dividing or slowly dividing cells, raising the prospect that they could be used to target neurons or stem cells.
They also insert themselves into the DNA of cells in such a way that may make them safer and able to produce more long-term effects than other potential gene therapy vectors, such as adenoviruses.
The researchers are now recruiting for a second trial of the treatment - dubbed VRX496.
This time it will be tested on patients whose HIV load is already well controlled by existing drugs.
The hope is that these patients will be able to stay off their antiretroviral drugs, which do have significant side effects, for an extended period.