Long-term HIV patient is effectively cured after stem cell transplant

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A 66-year-old man with HIV is in long-term remission after receiving a blood stem cell transplant with a rare mutation, raising the prospect that doctors could one day use gene editing to recreate the mutation and cure patients of the virus that causes AIDS, a medical team announced on Wednesday.

For now, the critical virus-destroying mutation is rare, making treatment unavailable to the vast majority of the 38 million patients living with HIV, including more than 1.2 million in the United States. Bone marrow transplants also carry significant risk and have only been used in HIV patients who have developed cancer.

The patient, who had lived more than half his life with the virus, is among a handful of people who went into remission after receiving stem cells from a donor with the rare mutation, said doctors at City of Hope, a cancer and research center. in Duarte, California, who treated him.

“This is a step on the long road to a cure,” said William Haseltine, a former professor at Harvard Medical School who founded the university’s cancer and HIV/AIDS research divisions. Haseltine, now president and chair of the nonprofit think tank Access Health International, was not involved in the City of Hope case.

While the announcement at the 24th International AIDS Conference in Montreal has no immediate implications for most people living with HIV, it continues the long, slow progression of treatment that began with the federal approval of the drug AZT in 1987, a decade later. with the use of protease inhibitors to reduce the virus in the body and went on to approve PrEP in 2012, which protects healthy people from infection.

As a result of those developments, an HIV patient diagnosed around age 20 today can receive antiretroviral therapy and live another 54 years, according to a 2017 study in the journal AIDS.

“When I was diagnosed with HIV in 1988, like many others, I thought it was a death sentence,” the City of Hope patient, who asked not to be identified, said in a statement shared by the hospital. . “I never thought that I would live to see the day that I no longer have HIV.”

The man received the transplant in early 2019, but continued to take antiretroviral therapy until he was vaccinated against Covid-19. He has been in remission for almost a year and a half.

“He’s doing a great job,” said Jana T. Dickter, an associate professor in the infectious disease division at City of Hope, who presented the data at the conference. “He’s in remission for HIV.”

Dickter said the patient is being treated for painful ulcers in his mouth caused by the donor’s stem cells attacking his tissue.

The patient received the transplant from an unrelated donor in 2019, after being diagnosed with acute myeloid leukemia. His doctor in City of Hope chose donor stem cells with a genetic mutation found in about 1 in 100 people of Northern European descent.

Those with the mutation, known as CCR5 delta 32, cannot be infected with HIV because it slams the door used by the virus to enter and attack the immune system. That passageway is the cell receptor CCR5, which the virus uses to enter the white blood cells that are an important part of the body’s defense against disease.

The City of Hope patient belongs to a small, select group of HIV patients who go into remission after such a transplant.

“This is probably the fifth case where this type of transplant appeared to cure someone. This approach clearly works. It’s curative and we know the mechanism,” said Steven Deeks, a professor of medicine at the University of California San Francisco who cared for the first such patient, Timothy Ray Brown. In 2007, Brown was cured by a medical team in Berlin using a transplant from someone who had… the same mutation.

After the transplant, Brown no longer had a detectable level of HIV in his blood. He was known as “the Berlin patient” until he let go of his name in 2010 and moved to San Francisco.

“I won’t stop until HIV is cured,” Brown swore in a 2015 essay in the journal AIDS Research and Human Retroviruses. Brown died in September 2020 of leukemia unrelated to his HIV. He was 54.

Similar successes followed in patients in London, Düsseldorf, Germany and New York.

“It’s another case similar to Timothy Brown from years ago,” emailed David D. Ho, one of the world’s leading AIDS researchers and director of the Aaron Diamond AIDS Research Center at Columbia University. “There are also several others, each of which uses approaches that are not feasible for most infected patients.”

The other patients also received bone marrow transplants, a relatively risky procedure in which the patient’s immune system is wiped out with chemotherapy drugs. Chemotherapy destroys remaining cancer cells, making room in the marrow for the donor cells and reducing the chance of them being attacked by the immune system. The transplanted blood stem cells are then injected into the bloodstream and make their way to the marrow, where – ideally – they begin to produce new, healthy blood cells.

While the survival rate for bone marrow transplant recipients has increased significantly, 30 percent of patients death within one year of surgery.

“I think it’s very possible to identify suitable donors, especially when more people register as bone marrow donors, with more representation from different racial and ethnic backgrounds,” said Eileen Scully, an associate professor of medicine at Johns Hopkins University School of Medicine. . “That way, this approach can be used for more people.”

But she added that “bone marrow transplantation is an important medical procedure that carries its own risks.”

City of Hope doctors said they had prepared the HIV patient for the transplant by giving him a lower-intensity chemotherapy developed by the cancer center and used in elderly patients.

HIV patients in rich countries such as the United States, where antiretrovirals are widely available, live longer, but are also at higher risk of developing certain cancers, such as leukemia. In addition, they have a higher risk of developing heart disease, diabetes, and even some brain disorders.

Dickter said when the City of Hope patient was diagnosed with acute myeloid leukemia in 2019, his doctors looked for a bone marrow match that contained the HIV-resistant mutation.

The nonprofit National Marrow Donor Program now routinely screens donors to find out if they have the CCR5 delta 32 mutation, said Joseph Alvarnas, a City of Hope hematologist-oncologist and a co-author of the abstract.

The ability to effectively cure many large numbers of people one day by using gene-editing techniques to generate the mutation may be a decade away, Deeks said.

Deeks said he is working with a San Francisco-based company called Excision BioTherapeutics to develop the first human trials that will edit the genes of patients with HIV. Studies have shown some success in gene editing in mice and monkeys infected with HIV.

Deeks said it’s not hard in the lab to use a gene-editing tool to disable the receptor that allows HIV to enter the immune system. Performing that task in a human patient’s body is where the work gets complex.

“That’s the challenge — to do that effectively and safely,” Deeks said. “And that’s a whole can of worms.”

Haseltine said researchers need to figure out how to get enough of the right cells in the body. At the same time, they must ensure that the treatment does not cause unwanted effects on other genes.

“The message to people living with HIV is that this is a signal of hope,” says Scully of Johns Hopkins. “It is feasible. It’s been recreated again. It is also a signal that the scientific community is really working to solve this puzzle.”

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