by A middle-aged woman with leukemia and HIVwhom scientists identify as the ‘New York patient’, has been free of the human immunodeficiency virus since 2017, after a transplant of virus resistant stem cells. The noveltyin this case, is that the mother cells come from blood of umbilical cord rather than from matched adult donors.
Preliminary results of the research were presented last year at an international conference, but the definitive study is published this week in the journal Cell. The work confirms the long-term effectiveness of this intervention, which is also attested to by the good health of the woman, who self-identifies as mestizo.
During a press conference, in which the research and clinical teams linked to the therapeutic procedure participated, the principal investigator Yvonne Brysonfrom the University of California in Los Angeles (UCLA), celebrated the “good news” that means that this woman is clinically healthy and “possibly cured”. In his words: “No virus is detected in blood with very sensitive tests. Today, she is free of both diseases”.
The successes of his process like those of the other counted people who have achieved the HIV remission in the world pave a promising therapeutic pathway. The previous one, which became known less than a month ago, was “the Düsseldorf patient”, a man who had been withdrawn from antiretroviral treatment against HIV under supervision after undergoing a stem cell transplant to treat a myeloid leukemia. Four years after that intervention, the virus had not reappeared, according to the article published at the time in the journal 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 the Berlin patient, in 2009, and the London one, in 2020, had been freed from the virus.
The three cases known to date correspond to stem cell transplants as part of their cancer treatmentsin which the cells donors invariably came from of compatible adults or “related” that carried two copies of the CCR5-delta32 mutation, one natural mutation that confers resistance HIV by preventing the virus from entering and infecting cells.
No virus is detected in blood with very sensitive tests. Today, she is clinically healthy, free of both diseases and possibly cured.
Yvonne Bryson
Now, the New York patient’s HIV remission joins this select group of people who do not have special immunological characteristics that allow them to control HIV infection Spontaneously. In these four casesthe virus has been cleared from the body as a result of a medical intervention and this differentiates them from the eradication by a functional cure in the so-called elite controllers or post-treatment (when the people’s own body presents special factors that allow them to stop the virus).
At the moment, scientists decline to estimate the time (in months or years) that has to elapse since the HIV is not detectable in blood until it can be declared that the cure is complete, since four patients still do not allow to elaborate statistics about.
Stem cell transplants with CCR5-delta32/32 cells offer a possible cure for HIV and blood cancer at the same time. However, due to invasive of the procedure, stem cell transplants (both with and without the mutation) are only being considered for people who need a transplant for other reasons, not to cure HIV in isolation; Before a patient can undergo a stem cell transplant, he needs to undergo chemotherapy or radiation therapy to destroy his immune system existing.
Umbilical cord blood in new therapies
At the press conference to disclose the results, Bryson highlighted the value of a treatment that opens the way “to continue studying this type of technique” in a broader way. “We are optimistic that one day stem cells from this particular source (umbilical cord blood) can be used to treat diseases other than cancer, and even adapt to different gene therapies”, he stressed.
However, the lead researcher insisted that there are “serious potentials complications linked to the transplants”, so it is about “procedures that they cannot be practiced to someone person with HIV”, but only “to those who need a transplant for a coexisting condition as serious as, in this case, leukemia”.
It is the fourth case in the world in which the virus has subsided as a result of a medical intervention.
In the case of “the New York patient”, moreover, it was known that it would be almost impossible to find a matched adult donor with the mutationso the team transplanted stem cells instead CCR5-delta32/32 carriers of cord blood stored (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).
Cells from the umbilical cord blood were infused along with stem cells from a relative of the patient to increase the chances of success of the procedure. “With umbilical cord blood, there are not as many cells available and they take a little longer to populate the body after infusion,” Bryson clarified in the article presenting the work. And he added that “using a mixture of stem cells from a matched relative of the patient and umbilical cord blood cells gives a boost to cord blood cells.”
The transplant managed to remit both the patient’s HIV and leukemia. 37 months after the transplant, the patient was able to stop taking the antiviral medication against HIV. The doctors, who continue to monitor her, state that the virus has not been detectable in her blood for more than 30 months since she stopped antiviral treatment.
Donors and racial diversity
Among the conclusions of the study on the New York patient, the researchers point out an apparently curious fact that the use of umbilical cord blood stem cells increases the potential to cure HIV through stem cell transplantation in people of “ all the racial origins”. The lead author of the study put it in the presentation: “The HIV epidemic is racially diverseand it is extremely rare for African-Americans and mixed-race people to find a sufficiently matched unrelated adult donor.”
The patient has spent more than 30 months without the virus being detectable in her blood since she stopped antiviral treatment
Nails 38 million people people around the world are living with HIV, and antiviral treatments, while effective, must be taken for life. Only about 1% of white people are homozygous (possessing two identical copies of a gene for a given trait) for the CCR5-delta32 mutation, a feature that is still rarer in other populations. This rarity limits the possibility of transplanting mother cells bearers of the beneficial mutation racialized patients, since stem cell transplants often require a high match between donor and recipient.
Bryson, who co-led the work with his colleague pediatrician and expert in infectious diseases Deborah Persaudof the Johns Hopkins University School of Medicine, explained: “The use of umbilical cord blood cells expands opportunities for people of diverse ancestry living with HIV who require a transplant for other conditions to achieve a cure.”
When asked by SINC, the UCLA researcher elaborated: “surely this case encourages finding more opportunities for racially diverse groups with HIV.” She added that in her service they have a record of “a significant number of racialized children in whom the possibility of using umbilical cord blood could help.” in different therapeutic treatments”. This effectively means “reaching a broader population than can be reached with donations from compatible adults.”
For her part, at the same press conference, Deborah Persaud highlighted the fact that “the New York patient” is “the Only Woman, among some 20 million women who live with this virus”, in achieving HIV remission after a therapeutic procedure. “This is very significant to give hope to everyone elseabove all, taking into account that she is a middle-aged and mixed-race woman,” according to her statements.
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 one. mutated cell population, and studies that transplanted new stem cells without this mutation have failed to cure HIV,” Persaud said. 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 to achieve remission for both.
The authors stressed at all times the need to make a greater effort for detect mutation CCR5-delta32 in donors and donations of stem cells. “With our protocol, we identified 300 units of umbilical cord blood with this mutation, so that if someone with HIV needed a transplant tomorrow, they would be available,” Bryson detailed. And he emphasized that “something must be done Continuously to search for these mutations, and this will require the support of communities and governments”.
Finally, at the press conference, Koen van Besienfrom the clinical team, indicated that “there are cord bases in more than a dozen countries, where mothers can voluntarily donate blood from the umbilical cords”, but that this is not enough and that more repositories are needed.
Reference:
Yvonne Bryson et al. “HIV-1 remission and possible cure in a woman after haplo-cord blood transplantation”. Cell (2023)
This article was first published on SYNC
