Study Gives Hope of Altering Genes to Repel H.I.V.

The idea of genetically altering people’s cells to make them resist the virus that causes AIDS may seem like a pipe dream, but a new report suggests it can be done.

The research involves the first use in humans of “gene editing,” a treatment that zeros in on a particular gene and disables it.

In 12 people infected with H.I.V., scientists used the technique to get rid of a protein on the patients’ immune cells that the virus must latch onto to invade the cells. Cells were removed from the patients, treated and then dripped back into their bloodstreams through an intravenous line.

In theory, if enough cells could be engineered to repel the virus, patients might no longer need antiviral drugs, and might in effect be cured.

The experiment was a pilot study, meant to test safety, not efficacy. It found that immune cells could be altered, and that doing so did not harm patients. The gene editing also seemed to help fight the infection in some cases, but the findings are preliminary and researchers cautioned that widespread use of the technique is a long way off.

“It’s a great strategy,” said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, who was not involved in the research. “It’s exciting, interesting, elegant science. But a lot of ‘ifs’ need to be addressed before you can say ‘Wow, this could really work.’ ”

Dr. Fauci also questioned whether patients would want this relatively complex treatment when many people can keep the infection under control with just one to a few pills a day.

An article about the study is being published on Wednesday in The New England Journal of Medicine, by researchers from the University of Pennsylvania, the Albert Einstein College of Medicine in New York and Sangamo BioSciences, a company in Richmond, Calif., that makes the gene-editing product.

The study has its roots in something that scientists discovered in the 1990s: A small percentage of people are resistant to H.I.V. thanks to a lucky mutation that causes their immune cells to lack CCR5, a protein that gives the virus a foothold. In people with one copy of the mutated gene, the infection progresses more slowly than in those who have normal CCR5. People who have inherited two copies of the mutated gene, one from each parent, are highly resistant to H.I.V. and may never become infected despite repeated exposure.

One man, known as “the Berlin patient,” was apparently cured of AIDS after he developed leukemia and had bone-marrow transplants in 2007 and 2008. As luck would have it, his bone-marrow donor had two copies of the mutated gene for CCR5. His immune system rebounded, the virus disappeared and he was able to stop taking antiviral drugs. But bone-marrow transplants are too arduous, risky and expensive to be used as a treatment for H.I.V.

Dr. Carl June, the senior author of the study and an expert in AIDS and cancer at the University of Pennsylvania, said gene editing may offer another way to achieve the same result.

He said the approach was worth considering because many patients dislike the antiviral drugs and experience side effects, and because lifelong treatment can cost $1 million in the United States. Gene editing could be cheaper, he said.

One scientific advance had a big role in making researchers consider even trying to engineer H.I.V. resistance: the development of a powerful molecular tool, zinc-finger nucleases, enzymes that can cut DNA at specific sites. When the cell tries to repair such a cut, it often makes mistakes, disabling that particular gene.

At first, he doubted that the technology would ever be useful for humans, but he began trying it out in mice, and was surprised by how well it worked.

“It’s incredible,” Dr. June said. “This tool can target any gene you desire.”

He and his team began testing the technique in people with H.I.V. in 2009. The 12 patients were given infusions of about 10 billion of their own CD4 T-cells, which had been treated to disable the CCR5 gene. The technique disabled the gene in 11 percent to 28 percent of the treated cells.

Six of the patients then stopped taking antiviral drugs. In most, their H.I.V. levels went up and their immune cells diminished. But the modified immune cells declined significantly less than the patients’ untreated cells, suggesting that the gene editing was protective. The altered cells persisted, at least for a while. On average, half were still present after 48 weeks.

Jay Johnson, 53, who lives in Philadelphia, took part in the study and was treated in 2010. He was the only patient who had an adverse reaction: a brief bout with fever, chills and joint and back pain.

For three months, he went off antiviral drugs. Initially, his virus levels were undetectable, but they began to rise, and he went back on the drugs.

A few months ago, doctors told him that he still had some of the altered cells, Mr. Johnson said, adding that he hopes the cells will keep multiplying, take over and eventually leave him virus free. He would gladly go through the treatment again, he said.

“If this works, it will be just such an overwhelming joy to say that I’m H.I.V. negative,” he said.

As the studies move ahead, Dr. June said, researchers will be trying to find ways to increase the proportion of edited cells and to make them persist in the body. It remains to be seen whether the treatment can be made practical for large numbers of patients. Because the test patients have received a treatment that alters their DNA, the Food and Drug Administration requires 15 years of follow-up to check for adverse effects. One concern is that the treatment could disable the wrong genes, though no evidence of that has been seen so far.

A version of this article appears in print on March 6, 2014, on page A4 of the New York edition with the headline: Study Gives Hope of Altering Genes to Repel H.I.V.