Gene Therapy for Controlling HIV Shows Early Promise
Small study hints treatment could someday help patients fight AIDS virus without drugs
By Amy Norton
WEDNESDAY, March 5, 2014 (HealthDay News) -- In an early step toward drug-free HIV therapy, researchers are reporting the first success in genetically "editing" T-cells in patients' immune systems to become resistant to the virus.
The findings, published in the March 6 issue of the New England Journal of Medicine, are based on only 12 patients. But experts were cautiously optimistic about what the study accomplished.
Specifically, researchers were able to take T-cells from the HIV patients' blood, then "knock out" a gene known as CCR5, which controls a protein that allows HIV to enter a cell.
The scientists then infused the genetically altered T-cells back into patients' blood, where they expanded in number. What's more, a few patients were taken off their HIV drugs temporarily and saw their virus levels decrease.
"This is impressive," said Rowena Johnston, director of research for amfAR, the Foundation for AIDS Research.
The altered T-cells "actually seem to be doing exactly what [the researchers] wanted them to," said Johnston, who was not involved in the study.
Still, she said, there are plenty of questions left and much research ahead. The investigators on the study agreed.
"This was a first-in-human study," said researcher Bruce Levine, an associate professor of cancer gene therapy at the University of Pennsylvania School of Medicine, in Philadelphia.
That means the trial was designed to see whether it's even safe to use this approach in people with HIV -- and not whether it's an effective therapy.
The T-cell infusions did appear safe in the short term: Of the 12 patients, only one had a temporary reaction -- developing fever, chills and joint pain within 24 hours of the infusion.
"Right now, we're at the point where we've demonstrated safety and feasibility," Levine said.
Ultimately, scientists want to develop a "functional" cure for HIV -- where people's immune system cells are resistant to the virus, and they can stop taking the lifelong, daily drug regimens currently used to suppress the infection.
Those drugs have turned HIV into a manageable chronic disease for many. But, Levine said, they are costly, cause side effects, and for some people, eventually lose their effectiveness.
No one knows whether the technology used in this study will eventually offer a functional cure. But Levine said there were "hints" that, with further refinement, it could.
One month after the T-cell infusion, half of the study patients stopped their regular HIV drug regimen for up to 12 weeks. Initially, the patients' "viral load" increased, but for the four who were able to stay off their medication for the full 12 weeks, the viral load declined toward the end.
There were also signs that some of the modified T-cells were resistant to HIV: When patients stopped their medications, the infused T-cells did decline in number -- but not to the extent that their unmodified T-cells did.