HIV patients for many years heal effectively after stem cell transplantation

So far, mutations that defeat serious viruses are rare, leaving treatment unavailable to the majority of 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 have developed cancer.

Patients who have lived with the virus for more than half of their lives are one of the few who have remitted after receiving stem cells from a donor with a rare mutation, a doctor in Hope, a cancer research center in California. Said. Duarte, California who treated him.

“This is a long way to cure,” said William Hasertin, a former Harvard Medical School professor who founded the University’s Cancer and HIV / AIDS Research Division. Haseltine, currently chairman and president of the non-profit think tank Access Health International, was not involved in the City of Hope case.

The announcement at the 24th International AIDS Conference in Montreal has no direct impact on most people living with HIV, but the long and slow progression of treatment that began with federal approval in 1987. Is continuing.Use of protease inhibitors to reduce viruses in the body, and further in 2012 PrEPPrevents healthy people from getting infected.

As a result of their development According to the report, HIV patients diagnosed around the age of 20 today can receive antiretroviral therapy and live for another 54 years. 2017 study With Journal AIDS.

“When I was diagnosed with HIV like many others in 1988, I thought it was a death sentence,” said a patient in Hope City who asked not to reveal his identity in a statement shared by the hospital. Said. “I never thought I would live to see the day when I was no longer infected with HIV.”

The man received a transplant in early 2019, but continued to receive 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 clinical professor of infectious diseases at the City of Hope, who presented the data at the conference. “He is in remission of HIV.”

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

The patient received a transplant from an unrelated donor in 2019 after being diagnosed with acute myeloid leukemia. His doctor at the City of Hope chose donor stem cells for which a gene mutation was found in about 1 in 100 people of Scandinavian descent.

People with a mutation known as CCR5-Delta 32 cannot be infected with HIV. This is to slam the doorways that the virus uses to invade and attack the immune system. Its gateway is the cell receptor CCR5, which is used by the virus to invade white blood cells. White blood cells form an important part of the body’s defense against disease.

Patients in the City of Hope are one of a small selected group of HIV patients who enter remission after undergoing such a transplant.

“This is probably the fifth case where this type of transplant seemed to cure someone. This approach works clearly. It’s curative and the mechanism is known,” said the University of California, San Francisco. Stephen Dikes, a professor of medicine at the school who took care of the first such patient, Timothy Ray Brown, said. In 2007, Brown was by the Berlin medical team. Same mutation.

After the transplant, Brown did not have a detectable level of HIV in his blood. He announced his name in 2010 and was known as a “patient in Berlin” until he moved to San Francisco.

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

Similar success continued with patients in London, Dusseldorf, Germany and New York.

“This is another case that resembles Timothy Brown many years ago,” said David D., one of the world’s leading AIDS researchers and director of the Aaron Diamond AIDS Research Center at Columbia University. I sent an email to Ho. “There are several others, each using an infeasible approach for most infected patients.”

Other patients also had a bone marrow transplant. This is a relatively dangerous procedure that involves clearing the patient’s immune system with chemotherapeutic drugs. Chemotherapy destroys the remaining cancer cells, creating space in the bone marrow for donor cells and reducing their chances of being attacked by the immune system. The transplanted blood stem cells are injected into the bloodstream and reach the bone marrow, where ideally they begin to produce new healthy blood cells.

Survival of bone marrow transplant recipients has increased significantly, but 30% of patients You will die within a year of the procedure.

Eileen Curry, associate professor of Johns Hopkins University School of Medicine, said: “This makes this type of approach available to more people.”

However, she added, “Bone marrow transplantation is an important medical procedure with its own risks.”

Citi of Hope doctors said HIV patients were prepared for transplantation by giving them a low-intensity chemotherapy regimen developed by the Cancer Center for use in older patients.

HIV patients in wealthy countries like the United States, If antiretroviral drugs are widely available, they will live longer, but they also have an increased risk of developing certain cancers, such as leukemia. In addition, there is an increased risk of developing heart disease, diabetes, and even some brain conditions.

According to Dicker, when a patient in the City of Hope was diagnosed with acute myeloid leukemia in 2019, his doctor searched for a bone marrow match containing an HIV resistance mutation.

The non-profit National Marrow Donor Program is currently conducting regular screenings to determine if donors carry the CCR5-Delta32 mutation, said Hope’s hematologist, oncologist and co-author of the summary. Joseph Albanas said.

One day, the chances of effectively treating so many people by using gene-editing techniques to generate mutations could be ten years away, Dikes said.

Dikes said he is working with a San Francisco-based company called Excision BioTherapeutics to develop the first human trial involving genetic editing of HIV patients. Studies have shown some success in editing genes in HIV-infected mice and monkeys.

Dikes said it wasn’t difficult In the lab, we use gene editing tools to knock out receptors that allow HIV to enter the immune system. Performing that task within the body of a human patient can be a complex task.

“That’s the challenge, it’s about doing it effectively and safely,” says Dikes. “And that’s the whole can of worms.”

Haseltine said researchers need to understand 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,” said Johns Hopkins Scully. “It’s feasible. It’s duplicated again. It’s also a sign that the scientific community is serious about solving this puzzle.”