The case of the first woman cured of HIV after stem cell transplantation is published

A middle-aged woman with leukemia and HIV, who scientists have identified as the ‘New York patient’, has been HIV-free since 2017 following a transplant of stem cells resistant to the virus. The novelty, in this case, is that the stem cells come from umbilical cord blood, and not from compatible adult donors.

Preliminary research results were presented last year at an international conference, but the definitive study was published this week in the journal Cell. The work confirms the long-term effectiveness of this intervention, which is also attested by the good health of the woman, who self-identifies as mestizo.

In a press conference, attended by research teams and clinics linked to the therapeutic procedure, the principal investigator Yvonne Bryson, from the University of California at Los Angeles (UCLA, USA), celebrated the “good news” that this woman is clinically healthy and “possibly cured”. In her words: “No virus is detected in the blood with very sensitive tests. Today, she is free of both diseases.”

Its good evolution, as well as that of the small number of people who have achieved HIV remission in the world, paves the way for this promising therapeutic route.

The previous one, known for less than a month, was “the patient from Düsseldorf”, a man who had been withdrawn from antiretroviral treatment against HIV under supervision after undergoing a stem cell transplant to treat myeloid leukemia. Four years after that intervention, the virus has not reappeared, according to the study published in Nature Medicine. This was the third case of a possible cure for HIV infection on a planetary scale, in which the body’s immune response against the virus was confirmed, despite having stopped receiving specific treatment.

Before the Düsseldorff patient, it had been confirmed that another in Berlin, in 2009, and in London, in 2020, had also gotten rid of the virus.

The three known cases so far correspond to stem cell transplants as part of their cancer treatments, in which the donor cells invariably came from compatible or “matched” adults who carried two copies of the CCR5-delta32 mutation, a natural mutation that confers resistance to HIV by preventing the virus from entering and infecting cells.

No viruses are detected in the blood with very sensitive tests. Today, she is clinically healthy, free of both illnesses and possibly cured.

Yvonne Bryson

Now, the HIV remission patient from New York joins that small group of cured people who lack special immunological characteristics that would allow them to spontaneously control their HIV infection. In these four cases, the virus was eliminated from the body by medical intervention and this differentiates them from eradication by functional cure in so-called elite controllers or post-treatment (when the person’s own body has special factors that allow it to stop the virus).

For the time being, scientists refuse to estimate the time (in months or years) that must elapse since HIV is not detectable in the blood until they can declare that the cure is complete, as four patients still do not allow statistics to be collected. compiled in in this regard.

Stem cell transplants with CCR5-delta32/32 cells offer a possible cure for HIV and blood cancer at the same time. However, due to the invasiveness of the procedure, stem cell transplants (both with and without the mutation) are only being considered for people who need a transplant for reasons other than to cure HIV alone. Before a patient can undergo a stem cell transplant, he needs to undergo chemotherapy or radiation therapy to destroy his existing immune system.

Umbilical cord blood in new therapies

At the press conference, Bryson highlighted the value of a treatment that paves the way for “continuing to study this type of technique” more widely. “We are optimistic that one day stem cells from this specific source (umbilical cord blood) could be used to treat diseases other than cancer and even be adapted to different gene therapies,” he said.

However, the principal investigator insisted that there are “potential serious complications linked to transplants”, which is why they are “procedures that cannot be performed on anyone with HIV”, but only “on those who need a transplant for a co-existing condition such as as serious as, in this case, leukemia”.

It is the fourth case in the world where the virus has subsided as a result of medical intervention.

Furthermore, it was known that it would be nearly impossible to find an adult donor compatible with the mutation in the “New York patient,” so the team transplanted CCR5-delta32/32-bearing stem cells from stored cord blood. (in cord blood banks) to try to simultaneously cure his cancer and HIV. The patient received the transplant in 2017 at Weill Cornell Medicine, thanks to a team of transplant specialists led by Jingmei Hsu and Koen van Besien. Her case was part of the International Maternal and Adolescent AIDS Clinical Trials Network (IMPAACT).

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Cord blood cells were infused together with stem cells from a patient’s relative to increase the chances of success of the procedure. “With cord blood, you don’t have as many cells and they take a little longer to populate the body after infusion,” Bryson clarified, “and they use a mixture of stem cells from a matched relative of the patient and cells from the blood of the umbilical cord. .umbilical cord gives the umbilical blood cells a boost.”

The transplant was able to resolve both the patient’s HIV and leukemia. 37 months after the transplant, the patient was able to stop taking the antiviral medication against HIV. Doctors, who continue to monitor her, say the virus has not been detected in her blood for more than 30 months, since she stopped antiviral treatment.

Donors and racial diversity

Among the study’s findings on the New York patient, the researchers note that the use of cord blood stem cells increases the potential for curing HIV through stem cell transplantation in people of “all racial backgrounds.” The lead author of the study put it in the presentation: “The HIV epidemic is racially diverse and it is extremely rare for African Americans and people of color to find a sufficiently matched unrelated adult donor.”

The patient has gone more than 30 months without the virus being detected in her blood since she stopped antiviral treatment.

About 38 million people worldwide are living with HIV, and antiviral treatments, while effective, must be taken for life. Only about 1% of whites are homozygous (having two identical copies of a gene for a given trait) for the CCR5-delta32 mutation, an even rarer trait in other populations. This rarity limits the possibility of transplanting stem cells carrying the beneficial mutation into racial patients, since stem cell transplants generally require a high match between donor and recipient.

Bryson, who co-led the work with fellow pediatrician and infectious disease specialist Deborah Persaud of the University of California School of Medicine. Johns Hopkins Universityexplained, “The use of cord blood cells expands opportunities for people of diverse ancestry living with HIV who need transplantation for other conditions to achieve a cure.”

When asked by SINC, the UCLA researcher elaborated, “Certainly this case encourages finding more opportunities for racially diverse groups with HIV.” In their service, they have a record of “a significant number of racialized children in whom the possibility of using umbilical cord blood in different therapeutic treatments could help”. That means “reaching a wider population than can be reached with matching adult donations.”

In turn, Persaud highlighted the fact that the “patient from New York” is “the only woman, among about 20 million women living with this virus”, to achieve HIV remission after a therapeutic procedure. “This is very significant to give hope to everyone else, especially considering that this is a middle-aged mixed-race woman,” she said.

Screen cells with the resistant mutation

“This study points to the really important role of having CCR5-delta32/32 cells as part of stem cell transplants for HIV patients, because all the successful cures so far have been with this mutant cell population, and the studies that transplanted new stem cells cells without this mutation were unable to cure HIV”, indicated Persaud. Hence the recommendation that, when performing a transplant as a cancer treatment for someone with HIV, the priority is to “look for cells that are CCR5-delta32/32”, to try for remission of both.

The authors have consistently emphasized the need for increased efforts to detect the CCR5-delta32 mutation in stem cell donors and donations. “With our protocol, we’ve identified 300 units of cord blood with that mutation, so if someone with HIV needed a transplant tomorrow, they would be available,” Bryson said, emphasizing, “Something needs to be done continually to look for these mutations, and that will require the support of communities and governments.

Finally, also during the press conference, Koen van Besien, from the clinical team, recalled that “there are cord bases in more than a dozen countries, where mothers can voluntarily donate blood from the umbilical cords”, but they are not enough and more repositories are needed.

Reference:

Yvonne Bryson et al. “HIV-1 remission and possible cure in a woman after haploid blood transplantation”. Cell (2023)

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