Following a cutting-edge treatment four years ago, the “New York patient” is now off of HIV medication and remains “asymptomatic and healthy,” researchers say.
A US research team reported that it may have cured HIV in a woman for the first time ever. Building on previous successes as well as failures in the HIV-cure research field, these scientists used a state-of-the-art stem cell transplant method that they hope will expand the pool of people who receive several dozen similar treatments annually. Can get it.
His patient has joined a rare club that includes three men who scientists have found to be cured, or very likely, cured of HIV. Researchers also know of two women whose own immune systems, exceptionally, apparently overcame the virus.
Karl Diefenbach, director of the AIDS division at the National Institute of Allergy and Infectious Diseases, one of several divisions of the National Institutes of Health that funds the research network behind the new case study, told NBC News that repeatedly won the clear. The accumulation of "continues to provide hope" in curing HIV.
"It is important that success continues along this line," he said.
In the first case ultimately deemed a successful HIV cure, investigators treated American Timothy Ray Brown for acute myeloid leukemia, or AML. They received a stem cell transplant from a donor who had a rare genetic abnormality that grants immune cells that HIV targets the virus' natural resistance. The strategy in Brown's case, which was first made public in 2008, has apparently cured HIV in two others. But it has also failed a string of others.
This medical procedure is to replace a person's immune system with another person's, to treat their cancer, as well as to treat their HIV. First, physicians must destroy the original immune system with chemotherapy and sometimes radiation. The hope is that it destroys as many immune cells as possible that still silently harbors HIV despite effective antiretroviral treatment. Then, provided the transplanted HIV-resistant stem cells attach properly, new viral copies that can proliferate from any remaining infected cells will be unable to infect any other immune cells.
It is unethical, experts insist, to attempt to treat HIV through stem cell transplantation -- a toxic, sometimes fatal procedure -- into someone who doesn't have a potentially fatal cancer or other condition that already exists. That makes it a candidate for such risky treatment.
A pediatric infectious disease specialist at the Johns Hopkins University School of Medicine, Dr. Deborah Persaud, who chairs the NIH-funded scientific committee behind the new case study (International Maternal Child Adolescent AIDS Clinical Trials Network), said that "as long as we're done talking about a new case of a potential cure for HIV." Very excited", the stem cell treatment method "is not a viable strategy for everyone except the millions of people still living with HIV."
Advancing the Envelope in HIV-Cure Science
A pediatric infectious disease specialist at UCLA's David Geffen School of Medicine, Dr. Yvonne J. Bryson described the new case study Tuesday at the Virtually-Held Annual Conference on Retroviruses and Opportunistic Infections.
The "New York patient," as the woman is being called as she received her treatment at New York-Presbyterian Weill Cornell Medical Center in New York City, was diagnosed with HIV in 2013 and leukemia in 2017.
Bryson and Persaud have partnered with a network of other researchers to conduct laboratory tests to evaluate the woman. At Weill Cornell, Dr. Jingmei Hsu and Dr. Koen van Bassien of the Stem Cell Transplant Program were joined by infectious disease specialist Dr. Marshall Glasby on patient care.
The team has long sought to ease the enormous challenge faced by investigators in finding a donor whose stem cells could cure a patient's cancer and cure their HIV.
Traditionally, such a donor must have enough human leukocyte antigen, or HLA, to maximize the chance that the stem cell transplant will engraft well. The donor must also have a rare genetic abnormality conferring HIV resistance.
This genetic abnormality occurs mainly in people of Northern European ancestry, and even in people native to that region, at a rate of only 1 percent. So for those who lack a sufficiently similar lineage, the chances of finding a suitable stem cell donor are particularly low.
In the United States, African-Americans make up about 40 percent and Hispanics make up about 25 percent of the roughly 1.2 million people with HIV; Whites comprise some 28 percent.
Sate-of-the-art treatment
The procedure used to treat the New York patient, known as a haplo-cord transplant, was developed by the Weill Cornell team to expand cancer treatment options for people with malformations of the blood. were developed for those lacking HLA-identical donors. First, the cancer patient receives a transplant of cord blood, which contains stem cells that amount to a powerful neonatal immune system. A day later, they receive a large graft of adult stem cells. Adult stem cells proliferate rapidly, but over time they are completely replaced by cord blood cells.
Compared to adult stem cells, cord blood is more adaptable, typically requires less of a close HLA match to be successful in cancer treatment and has fewer complications. However, cord blood usually does not produce enough cells to be effective as a cancer treatment in adults, so transplantation of this type of blood has traditionally been limited to pediatric oncology. In haplo-cord transplantation, additional transplantation of stem cells from an adult donor, which provides an abundance of cells, can help compensate for the lack of cord blood cells.
"The role of adult donor cells is to speed up the initial engraftment process and make transplantation easier and safer," Van Bassien said.
For a New York patient who has mixed-race ancestry, the Weill Cornell team and her colleagues found an HIV-resistant genetic abnormality in the cord blood of an infant donor. They combined the transplantation of those cells with stem cells from an adult donor. There was only a partial HLA match for both donor female, but the combination of the two transplants allowed for this.
"We estimate that there are about 50 patients per year in the U.S. who may benefit from this procedure," van Bassien said of the use of haplo-cord transplantation as an HIV-treating therapy. "The ability to use partially matched cord blood grafts greatly increases the chances of finding suitable donors for such patients."
Another advantage of relying on cord blood is that it is much easier to screen a large number of HIV-resistance abnormalities on the side of this resource than the bone marrow registries from which oncologists find stem cell donors. Before the New York patient became a candidate for the haplo-cord treatment, Bryson and her colleagues had already examined thousands of cord blood samples looking for a genetic abnormality.
The woman's transplant has been done very well. He has been in remission from his leukemia for more than four years. Three years after her transplant, she and her physicians stopped her HIV treatment. Fourteen months later, she still hasn't experienced any resurgent virus.
Many ultrasensitive tests cannot detect any signs in a woman's immune cells capable of replicating HIV, nor can researchers detect any HIV antibodies or immune cells programmed to go after the virus. Huh. They also pulled immune cells from the woman and attempted to infect her with HIV in a laboratory experiment - to no avail.
"Unless we were able to use cord blood cells, it would have been very difficult to find a match and this rare mutation," Dr. Bryson said at Tuesday's conference. "It opens this approach to greater diversity of the population."
Be alert
At this stage, Bryson and his colleagues consider the woman to be in a state of HIV remission.
"You don't want to over-call it," Bryson said of favoring the term "remission" over "cure" at this stage.
Case in point: Johns Hopkins' Deborah Persaud was the author of a case study she first presented in 2013 about a child in Mississippi who was at the time in what she called a "functional cure." Clearly infected with HIV from its mother in utero, the baby was treated with an unusually intense antiretroviral regimen shortly after birth. When Persaud announced the case study, the child was off HIV treatment for 10 months without a viral rebound. The news of this alleged HIV cure made a worldwide splash and created a frenzy in the media. But the child's virus recurred 27 months after her treatment was interrupted.
If enough time passes without any symptoms of the active virus - a few years - the authors of this latest case study would consider the New York patient cured.
"I'm excited that it turned out great for him," Bryson said. He said the case's apparent success has given researchers "more hope and more options for the future."
Why is HIV so difficult to treat?
When the highly effective combination antiretroviral treatment for HIV arrived in 1996, Dr. David Ho, one of the architects of this therapeutic revolution and director of the Aaron Diamond AIDS Research Center in New York City, famously theorized that given enough time . Such drugs can eventually eliminate the virus from the body.
To date, there are few cases who were started on antiretrovirals soon after contracting HIV, subsequently discontinued treatment and have remained in viral remission for years without any rebounding virus.
Otherwise Ho's prediction has turned out to be false. During the past quarter century, HIV-cure researchers have learned in increasingly precise detail how difficult it is to work not only to cure HIV, but to develop effective curative treatments that are safe and scalable.
HIV maintains such a permanent presence in the body because soon after infection, the virus divides its genetic code into long-lived immune cells that will enter a state of rest – meaning they can produce new viral copies. stop churning. Antiretrovirals only work on replicating cells, so HIV can remain under the radar of such drugs in resting cells for extended periods, sometimes years. In the absence of any HIV treatment, such cells can restart their engines at any time and reintroduce massive amounts of virus into the body.
The case of Timothy Brown, published in 2009, ignited an HIV-cure research field, which has since seen increasing financial investment.
In 2019, researchers announced two new cases of post-treatment HIV remission that Brown had received. These included Adam Castilejo, a London resident who had Hodgkin lymphoma, and a man in Düsseldorf, Germany, who had AML.
More than three years have passed since these two men have been weaned off HIV treatment without any viral rebound. As a result, the authors of each of their case studies – Ravindra K Gupta of the University of Cambridge and Dr Bjorn Jensen of Düsseldorf University Hospital – each recently told NBC News that their respective patient was "almost certainly" cured of the virus.
Since 2020, scientists have also announced cases of two women whose own immune systems have apparently cured them of HIV. They are about 1 in 200 people with HIV called "elite controllers" whose immune systems can substantially suppress viral replication without medication. In their cases, their bodies went even further and apparently destroyed all functional viruses.
A less toxic treatment
Another major advantage of the New York patient who received a haplo-cord transplant compared to the treatment of her three male predecessors, is that the use of cord blood – for reasons not fully understood – can be used as a graft vs. Known to greatly reduce the risk of host disease. This is a potentially devastating inflammatory response in which donor cells go to war with the recipient's body. Men experienced it in three other HIV-treated cases, which in Brown's case led to long-term health problems.
Brown died in September 2020 at the age of 54 from recurrent leukemia.
The New York patient was the second person with HIV to receive a haplo-cord transplant in hopes of a cure for the virus. However, the first person died of his cancer shortly after his 2013 treatment.
In contrast, the New York patient, Bryson said, remains "asymptomatic and healthy."