An American woman’s HIV infection appears to have cleared after receiving HIV-resistant stem cells. The treatment is a first: it is the first time that a so-called HIV leukemia treatment has been carried out with stem cells from umbilical cord blood.
Leukemia and HIV (human immunodeficiency virus) at the same time, that is not a good combination for anyone. However, there is also a small silver lining, because the treatment of leukemia sometimes requires a stem cell transplant. If the donor of these stem cells is selected properly, the transplant can cure HIV. That is probably happening in an HIV-positive woman of color with leukemia from the United States.
The woman, known as the New York patient, received a stem cell transplant in 2017 because of her leukemia. Normally, these stem cells come from an adult bone marrow donor, but in this transplant part of the stem cells came from umbilical cord blood. This was necessary because these cells in particular had the rare mutation that makes them resistant to HIV.
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After 37 months, the woman therefore stopped taking HIV inhibitors. This to see if the virus was still present in her body. That does not seem to be the case: since the woman stopped taking HIV inhibitors thirty months ago, no new HIV activity has been measured in her.
Genetics
Several people preceded the woman in her HIV remission, but they received different treatment. The stem cells used in their treatment came from bone marrow, not cord blood. But the same HIV-resistant version of the CCR5 gene was present in both the bone marrow stem cells and the cord blood stem cells. This so-called delta-32 mutation blocks HIV’s access to healthy cells.
In stem cell transplants, there must be a good match between the tissue type of the donor and the recipient. This lowers the risk of the recipient’s immune system attacking the new stem cells.
Since tissue types are hereditary, a person’s ethnicity affects their chances of finding a match. The gene mutation that leads to HIV resistance is very rare. It is only found in about 1 percent of white Northern European people and is much rarer in other populations.
Inexperienced stem cells
To find a donor for the New York patient, who is of mixed descent, doctors looked at another source of stem cells. Instead of bone marrow, they used stem cells from umbilical cord blood. A recipient does not have to fully match the donor’s tissue type to be eligible for these stem cells.
Arts Jingmei Hsu of New York Presbyterian Hospital explains why. In the case of umbilical cord blood, donor immune cells that come along with the stem cell transplant have less ‘experience’ (have encountered fewer viruses and bacteria) than with bone marrow cells from adult donors, she says. As a result, these cells react less violently to the body cells of the recipient.
When the donor’s immune cells, which come along during the transplant, do react violently to the recipient’s body, this is referred to as Graft versus Host Disease (GvHD). The risk of GvHD is lower with umbilical cord stem cell transplants than with bone marrow stem cells.
Mixed with the umbilical cord stem cells, the New York patient received bone marrow stem cells from a family member. It is difficult to filter enough stem cells from umbilical cord blood for a full stem cell transplant. By mixing the stem cells, the umbilical cord stem cells got a better start, says the doctor Yvonne Bryson of the University of California, Los Angeles, one of the principal investigators.
Rare combination
A stem cell transplant is not a good way to cure everyone with HIV. After a regular stem cell transplant, 15-20 percent of patients die. That while HIV does not have to be a deadly disease these days, if you take antiviral drugs.
Thus, stem cell transplants are only an HIV treatment option in very specific cases. ‘You have to be in good shape, because a bone marrow transplant is tough. You also have to have a very specific form of leukemia,’ says an infectious disease specialist Casper Rokx of the Erasmus Medical Center in Rotterdam. This was the case with the New York patient, who is now in remission from both HIV and leukemia.
For a stem cell transplant, the cells in your own bone marrow are first destroyed. After the transplant, the recipient is given drugs that suppress the immune system. This is to lower the risk of the recipient’s immune system attacking the new stem cells.
‘Because you start with few stem cells with umbilical cord blood, it takes longer until your new stem cells can produce new blood cells again. You are very susceptible to infections during the period in which your bone marrow is still recovering,’ says Rokx. ‘This is a very risky procedure that can only be used in very specific circumstances. So it’s great that such a specific case has been mapped out in this way.’
