A Southern California man appears to be cured of HIV after undergoing a stem cell transplant to treat leukemia, researchers reported this week at the International AIDS Conference in Montreal. While the risky procedure is not suitable for most people living with HIV, it offers clues for more feasible approaches.
"These cures are no longer anecdotal - we now have a real case series. That this approach is curative is no longer really questioned," Dr. Steven Deeks of UCSF told the Bay Area Reporter.
The man, dubbed the City of Hope Patient, was diagnosed with HIV in 1988, and his CD4 T-cell count fell so low that he was diagnosed with AIDS before starting antiretroviral treatment in the 1990s.
In early 2019, he received a stem cell transplant from a donor with a rare mutation, known as CCR5-delta-32, that blocks the virus from entering T-cells. Two years after the transplant, with an undetectable viral load, he and his doctors decided to stop his HIV treatment.
Now, three years after the transplant and more than 17 months after stopping antiretrovirals, he has not experienced viral load rebound and has no detectable HIV DNA, an indicator of hidden virus in cells. His leukemia also remains in remission, Dr. Jana Dickter of City of Hope Cancer Center in Duarte, California, reported at a media briefing.
The man, age 66, is older and has been living with HIV longer than the handful of other people previously cured after such a procedure, suggesting that this approach may be feasible for a wider subset of people with both HIV and cancer.
"The City of Hope Patient's case, if the right donor can be identified, may open up the opportunity for more older patients living with HIV and blood cancers to receive a stem cell transplant and go into remission for both diseases," Dickter said.
"When I was diagnosed with HIV in 1988, like many others, I thought it was a death sentence," the man, who wishes to remain anonymous, said in a City of Hope press release. "I never thought I would live to see the day that I no longer have HIV."
A handful of cures
Former San Francisco resident Timothy Ray Brown, known as the Berlin Patient, was the first person cured of HIV. His physician in Germany, Dr. Gero Hütter, came up with the idea to use cells from a donor with the CCR5-delta-32 mutation, speculating that it might cure both his leukemia and HIV.
Brown stopped antiretroviral treatment at the time of his first transplant, but his viral load did not rebound. Researchers extensively tested his blood and tissue samples, finding no evidence of functional HIV anywhere in his body. At the time of his death in September 2020, due to a recurrence of leukemia, he had been free of HIV for more than 13 years.
The second man to be cured, Adam Castillejo (known as the London Patient), underwent a stem cell transplant to treat lymphoma, receiving cells from a donor with the same mutation. He stopped antiretroviral treatment a year and a half after the transplant and has now been HIV-free for more than four years.
Earlier this year, researchers reported that a middle-aged woman in New York was free of HIV after receiving a combination of umbilical cord blood cells with the CCR5-delta-32 mutation and partially matched adult stem cells from a relative. She stopped antiretroviral treatment three years after the transplant, and her viral load remains undetectable a year and a half later.
A German man, dubbed the Dusseldorf Patient, reportedly has not experienced HIV rebound three years after stopping antiretroviral therapy post-transplant, but less is known about his case and it has not been widely reported in the media.
Researchers are not yet sure why these individuals were cured after stem cell transplants while other attempts have failed.
Prior to his transplant, Brown, then age 40, underwent intensive chemotherapy and radiation (known as conditioning therapy) to kill off his cancerous immune cells, allowing the donor stem cells to rebuild a new HIV-resistant immune system. But the donor cells attacked his body, resulting in near-fatal graft-versus-host disease.
Such a harsh conditioning regimen was not considered suitable for the City of Hope Patient, so he received reduced-intensity chemotherapy designed for older and less fit patients, Dickter said. Although the chemotherapy did not kill off all his existing immune cells, the HIV-resistant donor cells nonetheless appear to be doing the job.
Even with milder chemotherapy, stem cell transplants are too risky for people who do not need them to treat life-threatening cancer. What's more, the procedure is medically intensive and costly, and it would not be scalable to treat the millions of people living with HIV worldwide. But the new case adds more evidence that could lead to feasible cure approaches.
"These cases are still interesting, still inspiring and illuminate the search for a cure," International AIDS Society president-elect Dr. Sharon Lewin told reporters.
Researchers are exploring one potential strategy that uses gene therapy to snip out the genes that encode CCR5 receptors, hopefully leaving immune cells resistant to HIV.
"The key is to come up with a safer, more affordable and more scalable approach," Deeks told the B.A.R. "I am hopeful that with emerging gene editing technologies, we will one day leverage these cures for something that could have a global impact."
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