A transplant of stem cells from the umbilical cord has resulted in an American woman with leukaemia going into remission for HIV for the first time – having been cleared of HIV since 2017 – with the case providing hope for more high risk patients in the future.
The mixed-race woman, known as the New York patient, received HIV-resistant stem cells that had been harvested from umbilical cord blood to treat her leukaemia, reports the New Scientist.
Several people have previously gone into remission from HIV after receiving stem cells from adult donors who carry two copies of a naturally occurring mutation of the CCR5 gene. This delta 32 mutation prevents the virus from entering and infecting healthy cells.
With any stem cell transplant, recipients can only receive donations from people with matching tissue types to reduce the risk of their immune system attacking the transplanted tissue.
Since tissue types are inherited, a person’s ethnicity influences their ability to find a match. Having two copies of the CCR5 mutation is rare, existing in only around 1% of people of northern European ancestry, and being even rarer in other populations.
To overcome the lack of suitable adult donors, doctors carried out a study where they infused umbilical cord blood into the New York patient.
She also received stem cells from a relative. Umbilical cord blood can contain fewer stem cells than adult blood so mixing it with stem cells from a relative gives the cord blood a “kick start”, said Yvonne Bryson at the University of California, Los Angeles, who co-led the study, published in the journal Cell.
Using umbilical cord blood makes it easier to find transplant matches, as large repositories of frozen samples have been donated by people who gave birth in hospitals, says Jingmei Hsu at the New York Presbyterian Hospital.
“Having a bank (of cord blood) really opened the door to help more patients,” she says. Most people with HIV can lower the amount of the virus in their blood to undetectable levels by taking antiretroviral drugs, which stop the virus from replicating in their body.
Stem cell transplants would therefore only be considered for people with HIV who also have advanced blood cancer, which can be treated with the procedure. The New York patient no longer requires antiretroviral drugs and is also in remission for her leukaemia.
The transplant involves using chemotherapy, and sometimes radiation, to kill a person’s red blood cells, before infusing them with a donor’s stem cells. They are also given immunosuppressant drugs to reduce the risk of their immune system rejecting the transplant, which makes infections more likely.
It takes several months for the donor’s stem cells to repopulate the recipient’s blood cells, says Mario Stevenson at the University of Miami, Florida. “That window is a very high-risk window for the individual.”
The recipient’s body can also reject the transplant in a complication known as graft versus host disease (GvHD), when immune cells among the donated stem cells attack the recipient’s own cells.
With previous cases in which people with HIV went into remission after receiving adult stem cell transplants, some scientists believed that a relatively severe GvHD response was necessary to activate dormant HIV-infected cells so they could be more effectively eliminated, says Stevenson.
The New York patient, however, experienced only mild GvHD symptoms, like gastrointestinal discomfort, while still going into remission for HIV, he says. The other patients had more severe complications, such as hearing loss and extreme weight loss.
According to Hsu, the New York patient’s milder symptoms were probably due to the use of umbilical cord blood. This blood hasn’t been exposed to many toxins or infections, she says. Its T-cells, a type of immune cell involved in GvHD, are therefore less reactive to cells that may not be a perfect match, she says.
“With more success, like this story, we can open doors for all patients in these very, very high-risk situations,” says Hsu.
Study details
HIV-1 remission and possible cure in a woman after haplo-cord blood transplant
Jingmei Hsu, Koen Van Besien, Marshall J. Glesby, Deborah Persaud, Yvonne Bryson and
the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) P1107 Team
Published in Cell on 16 March 2023
Highlights
• First mixed-race woman with HIV-1 remission post CCR5Δ32/Δ32 haplo-cord transplant
• 100% immune reconstitution by CCR5Δ32/Δ32 cord graft and resistance to HIV strains
• No HIV viral rebound ≥18 months off antiretroviral therapy without graft vs. host disease
• No detectable HIV-1 DNA/RNA, replication competent virus & loss of HIV Ab response
Summary
Previously, two men were cured of HIV-1 through CCR5Δ32 homozygous (CCR5Δ32/Δ32) allogeneic adult stem cell transplant. We report the first remission and possible HIV-1 cure in a mixed-race woman who received a CCR5Δ32/Δ32 haplo-cord transplant (cord blood cells combined with haploidentical stem cells from an adult) to treat acute myeloid leukemia (AML). Peripheral blood chimerism was 100% CCR5Δ32/Δ32 cord blood by week 14 post-transplant and persisted through 4.8 years of follow-up. Immune reconstitution was associated with (1) loss of detectable replication-competent HIV-1 reservoirs, (2) loss of HIV-1-specific immune responses, (3) in vitro resistance to X4 and R5 laboratory variants, including pre-transplant autologous latent reservoir isolates, and (4) 18 months of HIV-1 control with aviremia, off antiretroviral therapy, starting at 37 months post-transplant. CCR5Δ32/Δ32 haplo-cord transplant achieved remission and a possible HIV-1 cure for a person of diverse ancestry, living with HIV-1, who required a stem cell transplant for acute leukaemia.
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