Woman cures HIV after innovative stem cell treatment

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A mixed race woman appears to be the third person in the world to have been cured of HIV. This has been achieved with a new transplant method involving cord blood, something that opens up the possibility of curing more people of diverse racial origin than has been possible until now, scientists announced Tuesday.

Umbilical blood is more widely available than the adult stem cells used in the bone marrow transplants that cured the two previous patients.

Also, it does not require such exact compatibility with the receiver. The majority of donors in the registries are of Caucasian origin. So, scientists said, the fact that the transplant can work even with only a partial match holds the potential to cure dozens of Americans a year who have both HIV and cancer.

The patient, who also had leukemia, received umbilical blood to treat her cancer. The blood came from a partially matched donor, rather than the more common practice of using a bone marrow donor of a similar race and ethnicity to the patient.

She also received blood from a close relative to give her body temporary immune defenses while the transplant took effect.

Researchers presented some of the details of the new case Tuesday at the Conference on Retroviruses and Opportunistic Infections in Denver.

The new patient’s gender and racial origin mark an important advance in the development of an HIV cure, the scientists said.

“The fact that she’s mixed-race and that she’s a woman is really important in terms of science and the impact on the community,” said Steven Deeks, an AIDS expert at the University of California at San Francisco who was not involved in the work.

HIV infection is believed to progress differently in women than in men. However, although women account for more than half of the world’s HIV cases, only 11% of participants in trials of cures are women.

Deeks said, however, that he does not anticipate the new approach becoming commonplace. “It’s about offering inspiration and possibly a roadmap,” he noted.

Strong antiretroviral drugs can control HIV, but a cure is crucial to ending the decades-long pandemic. Nearly 38 million people worldwide are living with HIV and about 73% of them are receiving treatment.

A bone marrow transplant is not a realistic option for most patients. These transplants are highly invasive and risky, which is why they are usually only offered to people with cancer who have exhausted all other options.

To date, there have only been two known cases of people being cured of HIV. Timothy Ray Brown, described as “the Berlin patient”, spent 12 years free of the virus, until he died of cancer in 2020. In 2019 another patient, later identified as Adam Castillejo, was said to have been cured of HIV, confirming that Brown’s case it was not a simple stroke of luck.

The two men received bone marrow transplants from donors carrying a mutation that blocks HIV infection. The mutation has so far been identified in only about 20,000 donors, most of whom are of northern European origin.

In previous cases, as bone marrow transplants replaced their entire immune system, both patients suffered heavy side effects, including a graft-versus-host reaction, in which the donor’s cells attack the recipient’s body. Brown nearly died after the transplant. Castillejo’s treatment was less intensive, but in the year after the transplant he lost nearly 70 pounds, developed hearing loss and survived multiple infections, according to his doctors.

In contrast, the woman in the most recent case was discharged from the hospital 17 days after the transplant and did not experience a graft-versus-host reaction, according to Dr. JingMei Hsu, her doctor at Weill Cornell Medicine. According to Hsu, the combination of umbilical blood and his relative’s cells may have spared him many of the brutal side effects of an ordinary bone marrow transplant.

“It was previously thought that the graft-versus-host reaction could be an important reason for curing HIV in previous cases,” commented Dr. Sharon Lewin, president-elect of the International Aids Society and not involved in the work. For her, the new results overturn that idea.

The patient, now past middle age (she declined to reveal her exact age to protect her privacy), was diagnosed with HIV in June 2013. Antiretroviral drugs kept her virus levels low. In March 2017 she was diagnosed with acute myeloid leukemia.

In August of the same year, she received umbilical blood from a donor with the mutation that blocks HIV from entering cells. But umbilical blood cells can take about six weeks to settle, which is why she also received partially matched blood stem cells from a first-degree relative.

The haploid cells — cells from a relative that match half of her chromosomes — bolstered the patient’s immune system until umbilical blood cells became dominant, greatly reducing the risk of the transplant, said Marshall Glesby, an infectious disease specialist at Weill Cornell Medicine in New York and a member of the research team.

“The transplant received from the relative is like a bridge that took the patient to the point where the umbilical blood could take over,” he said.

The patient chose to discontinue antiretroviral treatment 37 months after transplantation. Today, more than 14 months later, her blood tests still show no signs of HIV, and she does not appear to have detectable antibodies to the virus.

Experts said it was unclear exactly why stem cells from umbilical blood seem to work so well. One possibility is that they would be better able to adapt to a new environment, said Koen Van Besien, director of the transplant service at Weill Cornell.

“They are newborns – they are more adaptable,” he said.

It is also possible that umbilical blood contains elements in addition to stem cells that help the transplant work.

“Umbilical stem cells are attractive,” Deeks said. “There is something magical about these cells and possibly something magical about umbilical blood in general that has an added benefit.”

Translation by Clara Allain

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