For about a decade, scientists have had remarkable success curing some blood cancers by modifying a patient’s own immune cells to recognize and kill the malignant cells.
That same approach may help control H.I.V., among the wiliest of viruses, scientists will report on Tuesday. After a single infusion of immune cells engineered to recognize the virus, two people in a new study have suppressed their H.I.V. to undetectable levels, one of them for nearly two years.
The data is scheduled to be presented at a gene therapy conference in Boston, but the researchers shared an early copy with The New York Times.
The treatment is years, if not decades, from being widely available, but the study offers what scientists call “proof of concept,” and the tantalizing hope that a single shot could one day offer lifelong relief from H.I.V.
“It is inspiration and a potential road map to get to where we need to go,” said Dr. Steve Deeks, an H.I.V. expert at the University of California, San Francisco, who led the trial.
Other scientists were enthusiastic about the milestone.
“It’s truly amazing that they were able to accomplish this,” said Dr. Hans-Peter Kiem, an oncologist and gene therapy expert at the Fred Hutchinson Cancer Center in Seattle, who was not involved in the study.
H.I.V. requires lifelong control because the virus hides out in deep recesses of the body, and comes roaring back when it sees an opportunity. It also mutates easily to evade its attackers.
More than 40 million people are living with H.I.V. worldwide. About three-fourths of them take daily oral pills to keep the virus in check, and a much smaller proportion now receive injections every month or two. Several companies are developing longer-acting options, including weekly and monthly pills, and shots that could be given just once a year.
But scientists still aspire to develop “functional cures” that would effectively control H.I.V. over a lifetime, even if they do not eliminate it.
“People are really working hard on trying to cure it, and we’re making progress,” said James Riley, an immunologist at the University of Pennsylvania who is also modifying immune cells to control H.I.V.
Since the 1990s, many scientists have tried to modify immune cells called T cells to attack H.I.V., but those efforts were mostly unsuccessful. Some research teams lost interest after the arrival of powerful antiretroviral drugs soon after.
Cancer researchers soldiered on and succeeded in using the approach against blood cancers like leukemia.
“Cancer will always probably be the pioneer in this stuff, because of the incredible unmet medical need,” Dr. Riley said.
In the new study, scientists at Caring Cross, a nonprofit focused on developing affordable immunotherapies, engineered immune cells from each study participant to carry two molecules on the cell surface. Both molecules bind to H.I.V. and kill infected cells, but one also prevents the immune cells from becoming infected.
“It’s this dual nature of targeting — killing and protecting — that we think is the missing piece in terms of how this therapy works,” said Boro Dropulić, the executive director of Caring Cross, who developed the method.
The researchers extracted immune cells from each participant, modified the cells, then injected them back in. The participants stopped taking antiretroviral drugs the day of the infusion.
If a person does not take antiretroviral drugs, their H.I.V. levels typically soar within two weeks. But one person in the trial partially suppressed the virus for 12 weeks before rebounding. Two others were still in remission, 92 and 48 weeks after their infusion.
All three had begun receiving antiretroviral therapy within months of being infected. Three others who had lived with H.I.V. for longer before they were treated did not respond and needed to resume antiretroviral therapy. (A seventh participant showed signs of control seven weeks after infusion.)
Those details may be important. Those who were treated early in infection may have less H.I.V. sequestered in their body. Their immune system may also be less ravaged by the virus, and therefore more likely to rally when infused with the modified cells.
“Three out of three people with early disease doing some degree of control, to me, is the most provocative finding here,” Dr. Deeks said.
The two people with long-term response did show some blips of viral replication that quickly died down. That is to be expected as H.I.V. emerges from its reservoirs and is quashed by the immune cells.
Still, the results were exciting, several experts said.
The numbers in the study are very small but “these n-of-ones are so powerful because they encourage further research,” said Dr. Mike McCune, the head of a division at the Gates Foundation that supports innovation in H.I.V.
“For us, what what’s important is to make sure that we can go from an n-of-one to an n-of-a-million or more,” he said. “And the only way to do that is to engage companies that know how to make products.”
The foundation has not invested in work that involves removing immune cells and reinfusing them back into the individual. That approach is too invasive and expensive to reach the millions who will need it, Dr. McCune said. But it is actively pursuing scalable options.
Cancer researchers are already showing success altering the immune cells while they are still in the body, which should eventually be cheaper by orders of magnitude.
The direct injections could be produced “for less than $10,000 and then be off-the-shelf, meaning you can have them ready when a patient or person living with H.I.V. comes in,” Dr. Kiem said.
Other groups are working on broadly neutralizing antibodies, rare molecules that can disable a wide range of H.I.V. versions by targeting parts of the virus that do not mutate.
“If we can combine these two approaches, that really may be synergistic and provide a pathway to deliver something close to a functional cure long term,” Dr. Riley said.
Anticipating long-term needs, Caring Cross is working with organizations in Brazil, India and elsewhere to manufacture the products for cancer at much lower costs. The team is also refining the tools and approach for H.I.V. and plans to begin a bigger study later this year.
“This is a first-in-human approach,” Dr. Deeks said. “We often come up with new theories as we do this, and that’s what’s happening as we speak.”
