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A Third Person Living With HIV Has Been Cured by Transplant

In a first, a middle-aged woman has been in remission from HIV for 14 months after being treated for leukemia with transplants of adult stem cells and umbilical cord blood. If she remains off treatment without any hint of HIV, she would be only the third person in the world — after the Berlin Patient and the London Patient — to be cured through a transplant.

“Her own virus could not infect her cells,” said Yvonne Bryson, MD, chief of pediatric infectious diseases at the David Geffen School of Medicine at the University of California, Los Angeles, who presented the study at the Conference on Retroviruses and Opportunistic Infections (CROI) 2022 Annual Meeting, which both presenters and the audience attended remotely.

The middle-aged New York woman of mixed race, who has asked that her specific race and age not be shared to protect her privacy, was diagnosed with HIV in 2013 when she was still in the very early stages of infection. She started treatment immediately and quickly achieved an undetectable viral load. An undetectable viral load not only prevents someone from transmitting HIV to others but also reduces or eliminates HIV replication, which means fewer variants and less time for the virus to infiltrate cells where it can hide.

But in 2017, she was diagnosed with leukemia. As a last resort to cure her of the cancer, she received a combination of adult stem cells from a relative’s blood that closely matched her own and umbilical cord blood obtained from a cord-blood bank. That particular sample of cord blood was selected for its genetic mutation against the CCR5 receptor on immune cells, CD4 T cells. That mutation makes the immune system resistant to HIV.

The two previous HIV cures, of Berlin Patient Timothy Ray Brown and London Patient Adam Castillejo, also used stem cell transplantation with a CCR5 mutation, but theirs were bone marrow transplants. Bone marrow transplants are more arduous than cord blood transplants, which are commonly used in pediatric cancer treatment.

In this case, the physicians treating her used both.

“This allows the adult cells to accelerate and grow up until the cord blood takes over,” said Bryson. During her talk at CROI 2022, Bryson pointed to two types of data: First, she presented data showing the level of HIV in the patient’s blood. Soon after HIV diagnosis and treatment, her viral load dropped to undetectable levels. She had a spike of virus when she received the transplant, but then it went back to undetectable and has stayed that way ever since.

Meanwhile, following the transplant, her immune system started rebuilding itself using the new, HIV-resistant cells provided in the transplant. As her care team watched, no graft-vs-host disease (GVH), a common side effect of stem-cell transplants, emerged. In fact, the transplant went so well that she was discharged early from the hospital.

One hundred days after the transplant, the immune system contained within the cord blood had taken over. Her CD4 immune cells returned to normal levels a little more than a year after the transplant. By 27 months, she decided to stop all HIV treatment to see if the transplant had worked.

This was the real test. But as Bryson and colleagues continued to watch her HIV viral load and her CD4 counts and search for infectious virus, they didn’t find any. She tested negative for HIV by antibody test. Bryson grew 75 million of her cells in a lab to look for any HIV. None. Aside from one blip in detectable HIV DNA at 14 weeks, researchers never found HIV in the patient again.

“Her cells are resistant to HIV now — both her own strains and laboratory strains,” Bryson told Medscape Medical News. “It’s been 14 months since then. She has no rebound and no detectable virus.”

The presentation drew as raucous as praise gets in a virtual environment. The comments began pouring in.

“Impressive results,” wrote Jim Hoxie, MD, professor emeritus at the University of Pennsylvania. “Exciting case,” wrote Allison Agwu, MD, a professor of pediatrics at Johns Hopkins School of Medicine. And Dennis Copertino, a research specialist at Weill Cornell Medicine in New York City, wrote, “Thank you so much for translating this important cure strategy to people of color.”

Most donors with CCR5 mutations are White, Bryson said, suggesting that this approach, in a mixed-race woman, could expand the pool of people living with HIV and cancer who are good candidates for the approach.

But other observers had questions, ones that may require more research to answer. Some asked why this woman’s virus, after transplantation, wasn’t just immune to viruses with CCR5 but also another variant, called CXCR4, that one wouldn’t expect. Luis Montaner, DVM, director of the Immunopathogenesis Laboratory at the Wistar Institute in Philadelphia, wondered whether it was more than the blood that had cleared HIV. Did it get into the tissue, too? That question has not yet been answered.

For Carl Dieffenbach, PhD, director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, the lack of GVH disease was a powerful and hopeful finding.

“There’s been this ongoing hypothesis that maybe graft-versus-host disease was needed at some level to help clear out every last single CD4+ T cell that may or may not have been harboring replication-competent virus,” Dieffenbach told Medscape Medical News. “But there was no GVH disease. That’s incredible. It’s a wonderful thing.”

Now the challenge is to move from a single case to making cure available to other people living with HIV.

The case also got cure researchers thinking.

Montaner called the case “an encouraging roadmap supporting anti-CCR5 strategies by CRISPR Cas9,” studies that are now underway. Steven Deeks, MD, called the case “perhaps a model for how we might do this using a person’s own cells. Because we were never really going to be transplanting cells from another person as a scaleable cure.”

For people living with HIV, particularly women of color, the results raise hopes and questions. Nina Martinez knows something about being a “first.” In 2019, she was the first American woman of color living with HIV to donate a kidney to another person living with the virus. To her, the excitement over the first woman of color being cured of HIV just shines a light on how very White and male HIV cure studies have been until now.

“For me, I’m not looking for a cure in which the successful step forward is me getting cancer,” she told Medscape Medical News. “I’m looking at, what’s going to be sustainable? I want to know what’s going to work for a group of people.”

Gina Marie Brown, a social worker living with HIV in New Orleans, is also thinking of groups of people.

“Every time we get a breakthrough, it’s like the sun is taken from behind the clouds a little more,” said Brown. “I think about people in the South, who bear a huge burden of HIV. I think about trans women. I think about Black women, and gay, bisexual, and same-gender-loving men. This could really impact HIV — in the same way that PrEP [preexposure prophylaxis] has, the same way that one pill once a day has.”

When Brown was diagnosed with HIV 22 years ago, she started to plan her funeral.

“That’s how much I thought HIV was a death sentence,” she told Medscape Medical News. “Oh my goodness! Glad you stuck around, Gina.”

The study was funded by the National Institutes of Health. Bryson, Dieffenbach, Deeks, and Montaner have disclosed no relevant financial relationships.

Conference on Retroviruses and Opportunistic Infections (CROI) 2022 Annual Meeting: Abstract 65. Presented February 15, 2022.

Heather Boerner is a science journalist based in Pittsburgh, PA. Her book, Positively Negative: Love, Pregnancy, and Science’s Surprising Victory Over HIV, came out in 2014.

For more news, follow Medscape on Facebook, Twitter, Instagram, and YouTube.

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