A long-term HIV patient can effectively recover after a stem cell transplant

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

So far, the critical mutation that defeats the virus is rare, making the vast majority of the 38 million people living with HIV, including more than 1.2 million in the United States, untreatable. Bone marrow transplants also carry significant risks and are only used in HIV-infected patients with cancer.

A patient who has lived with the virus for more than half his life is among several people who have gone into remission after receiving stem cells from a donor with a rare mutation, doctors at the City of Hope Cancer and Research Center said. He was treated by Duarte, California.

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

Although the announcement at the 24th International AIDS Conference in Montreal did not have an immediate impact for most people living with HIV, it continues the long and slow progress of treatment that began in 1987 with the federal approval of the drug AZT. went further with the use of protease inhibitors to reduce the virus in the body and in 2012 the approval of PrEP, which protects healthy people from infection.

As a result of those events According to a 2017 study in the Journal of AIDS, a patient diagnosed with HIV today at around age 20 could live another 54 years on antiretroviral therapy.

“When I was diagnosed with HIV in 1988, like everyone else, I thought it was a death sentence,” the hospital said in a statement. “I never thought I’d see a day when HIV wouldn’t exist.”

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

“He’s doing great,” said Jana T. “He’s in remission from HIV.”

According to Dicker, the patient is being treated for sores in his mouth caused by the donor’s stem cells attacking his tissue.

The patient received a transplant from an unrelated donor after being diagnosed with acute myelogenous leukemia in 2019. Her doctor in City of Hope selected donor cells from one in 100 people of northern European descent who had the genetic mutation.

People with the mutation, known as CCR5-delta 32, cannot get HIV because it closes the door the virus uses to enter and attack the immune system. That door is the CCR5 receptor cell, which the virus uses to enter white blood cells, which are an important part of the body’s defense against disease.

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

“This is probably the fifth time this type of transplant has cured someone. This method works clearly. It’s therapeutic and we know the mechanism,” said Stephen Dix, a professor of medicine at the University of California, San Francisco, who treated the first such patient, Timothy Ray Brown. In 2007, Brown was cured by a medical team in Berlin with the help of a transplant from a patient same mutation.

After the transplant, Brown’s blood was undetectable for HIV. He was known as the “Berlin Patient” before making his name in 2010 and moving to San Francisco.

“I will not stop until HIV is cured,” Brown vowed in 2015 in the journal AIDS Research and Human Retroviruses. Brown died in September 2020 of leukemia unrelated to HIV. He was 54 years old.

Similar successes have been seen in patients in London, Dusseldorf, Germany and New York.

“This is another story similar to Timothy Brown a few years ago,” wrote David D. Ho is one of the world’s leading AIDS researchers and director of Columbia University’s Aaron Diamond Center for AIDS Research. “There are also several others, each using methods that are not available to most infected patients.”

Other patients have also received bone marrow transplants, a relatively risky procedure that involves destroying the patient’s immune system with chemotherapy drugs. Chemotherapy destroys any remaining cancer cells, making room for donor cells in the marrow and making it less likely to be attacked by the immune system. The transplanted blood stem cells are then injected into the bloodstream and travel to the marrow, where – ideally – they begin to produce new, healthy blood cells.

Although the survival rate of bone marrow transplant recipients has improved significantly, 30 percent of patients dies within a year after the procedure.

“I think it’s important to identify suitable donors, especially as more people of different racial and ethnic backgrounds register as bone marrow donors,” said Eileen Scully, associate professor of medicine at the Johns Hopkins University School of Medicine. “It makes this type of approach available to more people.”

But he added, “a bone marrow transplant is a serious medical procedure that carries its own risks.”

Doctors in the City of Hope said they prepared the HIV patient for a transplant by giving him a low-intensity chemotherapy regimen developed by the cancer center and used with older patients.

In rich countries like the United States, people living with HIV People live longer in places where antiretroviral drugs are widely available, but they have a 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 diseases.

When a City of Hope patient was diagnosed with acute myelogenous leukemia in 2019, her doctors looked for bone marrow that contained an HIV-resistant mutation, Dicker said.

The nonprofit National Marrow Donor Program now routinely screens donors for the CCR5-delta 32 mutation, said Joseph Alvarnas, MD, a hematologic oncologist in Hope and an author of the paper.

According to Dix, the possibility of effectively curing many people someday using gene-editing techniques to induce mutations could be ten years away.

Dix said he is working with Excision BioTherapeutics, a San Francisco-based company, to develop first-in-human trials involving gene editing in HIV patients. Research has shown some success in editing genes inside HIV-infected mice and monkeys.

Deeks said it wasn’t difficult using a gene-editing tool in the lab to destroy the receptor that allows HIV to enter the immune system. Performing this task in the body of a human patient becomes more complicated.

“The challenge is to do it efficiently and safely,” Dix said. “That’s a whole can of worms.”

Haseltine says researchers need to figure out how to get to the right cells inside the body. At the same time, they need to ensure that the treatment does not cause unwanted consequences for other genes.

“Notifying people living with HIV is a sign of hope,” Johns Hopkins Scully said. “It is possible. It happened again. It’s also a sign that the scientific community is really trying to solve this puzzle.”

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