A transplant of stem cells from the umbilical cord has resulted in a mixed-race woman going into remission for HIV for the first time.
The woman, known as the New York patient, has been clear of detectable HIV since 2017, after she received HIV-resistant stem cells that had been harvested from umbilical cord blood to treat her leukaemia. Stem cells are produced by bone marrow and can turn into different types of blood cells.
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 that their immune system will attack 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 per cent 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, who identifies as mixed race.
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”, Yvonne Bryson at the University of California, Los Angeles, who co-led the study, said in a statement.
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 the individual with a donor’s stem cells. The recipient is 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, such as 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.
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