Is Umbilical Cord Blood Transplant a Feasible Treatment for HIV? | by heidi

Is Umbilical Cord Blood Transplant a Feasible Treatment for HIV? | by heidi


     


    A mixed-race woman has become the third person to be potentially cured of HIV. The patient received a new transplant of stem cells from an infant’s umbilical cord blood that carries a mutation resistant to the virus.



    The transplant, if proven to be successful in the long term, could broaden the opportunities for HIV treatment to people of various racial backgrounds.


    When the woman needed a stem cell transplant to treat her leukemia, doctors saw an opportunity to find a cord blood donor with natural immunity to HIV to help her overcome both diseases. This is the first time cord blood has been used to treat HIV.


    More than a year after the transplant, the researchers observed no HIV plasma in the woman’s system, even after going off her HIV antiretroviral medications. She has been in remission for her leukemia for more than four years.


    Scientists announced their findings last week at the Conference on Retroviruses and Opportunistic Infections in Denver, Colorado. There’s still a small chance that the infection could rebound, said Yvonne Bryson, MD, chief of pediatric infectious diseases at the David Geffen School of Medicine at UCLA who presented the case at the conference. Still, the patient’s remission is cause for optimism.



    “She today fulfills the profile of HIV remission as previous reports of cure,” Bryson said in a press briefing last week.



    How the Cord Blood Transplant Works

    To execute the transplant, health providers first destroy the patient’s bone marrow and cancer cells using radiation or high doses or anticancer drugs. They then introduce healthy stem cells from the donor with the hope they will replace the unhealthy cells without complications.


    Both umbilical cord blood and bone marrow contain the stem cells needed for this operation. Cord blood is more widely available and less invasive than bone marrow transplants, which cured the previous two patients. When using bone marrow, the patient must receive blood from a donor who matches them genetically, including by race and ethnicity.



    Since cord blood transplant only requires a partially matched donor, it opens up the potential to cure a more diverse array of people living with HIV and cancer.

    The donor in this case carried a gene mutation called CCR5-delta32/32 homozygous. This mutation hampers HIV’s ability to infect immune cells.



    This mutation is rare in adult stem cell donors. It can be found in about 1% of donors of Northern European descent and is even rarer in people of other backgrounds. If the team had sought an adult stem cell donor for this patient, there would be a “distinctly very low chance” for finding the right match, Bryson said.

    Taking a Mixed Approach

    The cord blood, which typically only contains enough cells for pediatric transplants, was supplemented with “haploidentical,” or half-matched blood, from the patient’s adult relative.

    In a process called engraftment, these adult cells began to grow and create healthy blood cells more quickly. This provided coverage for the first month while waiting for the cord blood cells to engraft. A hundred days after the transplantation, 100% of the cord blood cells were engrafted, creating what Bryson called “basically a new HIV-resistant immune system.”

    Bryson said her team learned from a case in Boston, in which the patient’s HIV rebounded. It’s not enough, she said, to just destroy the HIV-infected cells—providers must also replace them with cells that carry an HIV-resistant mutation.


     Discover the Ways Engraftment Shows a Successful Stem Cell Transplant

    “They used a kind of short-term, long-term strategy,” Jessica Justman, MD, an associate professor of medicine at the Columbia University Mailman School of Public Health specializing in HIV epidemiology, who was not involved in the research, told Verywell. “They wanted her to be engrafted with the cord stem cells that have the Delta 32 mutation in the long term. But they knew that was going to take a long time to work, so they gave her the haploidentical stem cell transplant that basically got her through the short-term period.”


    This patient never developed graft-vs-host disease, a complication of bone marrow or stem cell transplants which can arise when the cells of the donor see the cells of the recipient as foreign and launch an immune attack.


    She is clinically well and has had no HIV plasma remission.

    Is This Treatment Scalable?

    Stem cell transplantation is not an HIV-specific treatment. But for patients undergoing therapy for certain cancers and living with HIV, it may be able to treat both diseases.

    If this approach is proven to be effective at curing HIV, Bryson estimated that about 50 people per year would benefit from it. Screening cord blood banks for the HIV-resistant mutation could allow clinicians to make use of this previously untapped resource for people who have a hard time finding a genetic match among adult donors.

    Still, bone marrow and stem cell transplants are particularly risky and resource-intensive operations—ones that are only approved in cases of cancer and other life-threatening diseases. Plus, this case only demonstrated efficacy on a singular patient. To indicate it’s feasible for a broader population would require much more research.

    Justman, whose work focuses on HIV prevention and treatment, said the success of a stem cell transplant may not translate to most patients. The transplant relies on the patient’s ability and willingness to follow through on a treatment course that requires many intensive operations and follow-ups.


    “A bone marrow transplant or a stem cell transplant is not scalable,” Justman said. “It won’t make a dent in a global population of people living with HIV.”


    But this work, she said, opens up HIV treatment research to more innovate approaches.


    “This is important not because of its impact at a population level—it’s important because of its impact at a conceptual level,” Justman said. “It’s possible that this cure research will spark ideas that will bring us further down the road towards something that could be scalable.”

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