In the US, they were able to cure a patient with HIV using stem cells with a rare mutation

A 66-year-old man, a longtime HIV patient, is successfully treated after a stem cell transplant, but this is not an option for most people with the virus, reports Washington Post.

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The patient is in long-term remission after receiving a blood stem cell transplant containing a rare mutation, raising the possibility that doctors will one day be able to use gene editing to recreate the mutation and cure patients of HIV.

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At the moment, the crucial mutation that defeats the virus is rare, so treatment is out of reach for 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 risks and have only been used in HIV patients who developed cancer.

The patient, who has lived more than half of his life with the virus, is among the few people who have gone into remission after receiving stem cells from a donor with a rare mutation, said doctors at the City of Hope, the Duarte, Calif., cancer research and development center that treated him.

"This is one step on a long road to a cure," said William Hazeltine, a former professor at Harvard Medical School who founded the university's cancer and HIV/AIDS research departments. Haseltine, current chairman and president of the nonprofit think tank Access Health International.

While the announcement made at the 24th International AIDS Conference in Montreal has no immediate implications for most people living with HIV, it continues the long and slow process of treatment that began with the federal approval of AZT in 1987. The use of protease inhibitors to reduce the amount of virus in the body. Doctors went further in 2012 when PrEP was approved to protect healthy people from infection.

According to a 2017 study in the journal AIDS, as a result of these events, a patient with HIV who has been ill for about 20 years can receive antiretroviral therapy and live another 54 years.

“When I was diagnosed with HIV in 1988, like so many others, I thought it was a death sentence,” the patient said. “I never thought I would see the day when I no longer had HIV.”

The man received a transplant in early 2019 but continued to take antiretroviral therapy until he received a COVID-19 shot. Almost a year and a half in remission.

“He's doing great,” said Jana T. Dikter, a professor in the division of infectious diseases who presented the data at the conference. “He is in remission for HIV.”

Dikter said the patient is being treated for painful mouth ulcers caused by donor stem cells attacking his tissues.

A City of Hope patient received a transplant from an unrelated donor in 2019 after being diagnosed with acute myelogenous leukemia. His doctor selected 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 through which the virus enters and attacks the immune system. This entry is the CCR5 cellular receptor, which the virus uses to enter white blood cells, which are an important part of the body's defense against disease.

The patient is one of a small select group of HIV patients who go into remission after such a transplant.

“This is probably the fifth time this type of transplant has cured someone. This approach clearly works. It's a cure, and we know the mechanism," said Stephen Dix, professor of medicine at the University of California, San Francisco, who treated the first such patient, Timothy Ray Brown. In 2007, a team of doctors in Berlin treated Brown with a transplant from a person with 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 announced his name in 2010 and moved to San Francisco.

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

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

“This is another case that is reminiscent of Timothy Brown many years ago,” David D. Ho, one of the world's leading AIDS researchers and director of the Aaron Diamond AIDS Research Center at Columbia University, wrote in an email. “There are several others, all of which use approaches that are unacceptable for most infected patients.”

Other patients have also received bone marrow transplants, a relatively risky procedure that involves destroying a patient's immune system with chemotherapy drugs. Chemotherapy destroys remaining cancer cells, frees up space in the bone marrow for donor cells, and reduces the chance that they will be attacked by the immune system. The transplanted blood stem cells are then injected into the bloodstream and travel to the bone 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 die within a year of the procedure.

“I think it's quite possible to find suitable donors, especially as more people sign up to donate bone marrow, with more people representing different races and ethnicities,” said Eileen Scully, assistant professor of medicine at Johns Hopkins University School of Medicine. “This will allow this type of approach to be used for more people.”

But she added that "bone marrow transplantation is an important medical procedure that comes with certain risks."

City of Hope doctors said they prepared the HIV patient for transplant by giving him a less intensive chemotherapy regimen developed by the cancer center and used for older patients.

HIV patients in wealthy countries such as the US, where antiretrovirals are widely available, live longer, but they 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 diseases.

Dikter said that when a City of Hope patient was diagnosed with acute myelogenous leukemia in 2019, his doctors looked for bone marrow containing an HIV-resistant mutation.

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

The possibility of someday effectively treating large numbers of people with gene-editing techniques to create a mutation could be a decade away, Dix said.

Dicks said he is working with San Francisco-based Excision BioTherapeutics to develop the first human trials that will involve editing the genes of HIV patients. Research has shown some success in editing genes inside mice and monkeys infected with HIV.

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Dix said it's not difficult in a lab to use a gene-editing tool to disable the receptor that allows HIV to enter the immune system. Performing this task inside the body of a human patient becomes a challenge.

"It's a challenge to do it efficiently and safely," Dix said. “And it is very difficult.”

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

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