A team of American researchers reported that they may have successfully cured HIV in a woman. These scientists utilized a cutting-edge stem-cell transplant technique that builds on previous successes and failures in HIV-cure research. They expect to increase the number of people who can receive similar treatment to several dozen each year.
The patient was able to enter a rare club which includes three HIV-positive men. Researchers know of two women who have apparently beaten the virus with their own immune systems.
Carl Dieffenbach is the director of the Division of AIDS, National Institute of Allergy and Infectious Diseases. He told NBC News that the "continues the hope" that the numerous apparent victories in curing HIV has provided.
He stated, "It is important that there continue to be success along these lines."
The first case of what was eventually deemed a successful HIV cure involved the treatment of Timothy Ray Brown, an American, for acute myeloidleukemia (or AML). A stem cell transplant was performed from a donor with a rare genetic abnormality. This gives the immune cells in the body the ability to target natural resistance against the virus. Brown's strategy, first published in 2008, appears to have cured HIV in two others. It has also failed in a number of other cases.
This therapy is intended to replace the individual's immune system by another person, thus treating their HIV and also treating their cancer. First, doctors must destroy the immune system using chemotherapy or radiation. This will hopefully also kill as many HIV-positive immune cells as possible, even if they are receiving effective antiretroviral therapy. If the HIV-resistant stem cells transplanted successfully engraft, any new viruses that may emerge from infected cells won't be able to infect other immune cells.
Experts stress that it is not ethical to try an HIV cure via stem cell transplant. This can be fatal and toxic.
Dr. Deborah Persaud is a pediatric infectious diseases specialist at Johns Hopkins University School of Medicine. She chairs the NIH-funded scientific panel behind the new case study. The International Maternal Pediatric Adolescent AIDS Clinical Trials Network funded case study said that while "we're very excited about the new case of potential HIV cure", the stem cell treatment method "still cannot be a viable strategy for all but a few of the millions of HIV-positive people."
Advancing HIV-cure science
Dr. Yvonne J. Bryson is a UCLA pediatric infectious disease specialist. She presented the case Tuesday at the Conference on Retroviruses & Opportunistic Infections.
The woman, known as "New York patient", was diagnosed with HIV in 2013. She also had leukemia in 2017.
Persaud and Bryson have joined forces with other researchers to perform lab tests on the woman. Weill Cornell's stem cell transplant program has Dr. Jingmei Hsu, and Dr. Koen Van Besien. Dr. Marshall Glesby is the infectious disease specialist.
The team has been working for years to alleviate the significant challenge investigators face when trying to find a donor stem cell that could be used to treat cancer or cure HIV.
To maximize the chances of stem cell transplant success, a donor must be close to the human leukocyte antigen (or HLA) match. A rare genetic abnormality must be present in order to confer HIV resistance on the donor.
This genetic anomaly is most common in people of northern European descent, as well as people from that region, at a rate around 1 percent. The chances of finding a donor stem cell for someone with a similar genetic background are very low.
The United States has approximately 1.2 million HIV-positive people. Hispanics make up about 40% and African Americans about 25%, respectively. Whites are at 28%.
The Weill Cornell team developed the procedure to treat the New York patient. It is known as a Haplo-cord Transplant. This was done to expand the options for those with blood malignancies that are not HLA-identical donors. The cancer patient first receives umbilical cord blood. This contains stem cells that can help build a strong immune system. The patient receives a larger graft with adult stem cells a day later. Adult stem cells grow rapidly but are eventually replaced completely by cord blood cells.
Cord blood is more flexible than adult stem cells and requires a closer HLA match to be able to treat cancer. It also causes fewer complications. However, cord blood does not usually yield enough cells to make a treatment for cancer in adults. Therefore, transplants of cord blood have been limited to pediatric oncology. The addition of stem cells from an adult donor can be used to compensate for the lack of cord blood cells in haplo-cord transplants. This allows for a greater number of cells and can also help to make up the difference.
Van Besien stated that the role of adult donor cells was to accelerate the early engraftment and make the transplant safer and easier.
The Weill Cornell team found the HIV-resistant genetic abnormality within the umbilical cord blood from an infant donor. This was a major concern for the New York patient. They combined the stem cells of an adult donor with those cells to create a combination transplant. Although the HLA matches between the donors and the woman were not perfect, the combination of both transplants enabled this.
Van Besien stated that the haplocord transplant could be used as an HIV-cure therapy. "We estimate there are approximately fifty patients per year in America who could benefit from it." "The possibility of using partially matched umbilical cord blood donors greatly increases the chances of finding suitable donors."
One advantage of using cord blood for stem cell donation is the fact that it is easier to screen large numbers of these resources for HIV-resistance abnormalities than bone marrow registry databases. Bryson and her colleagues had already screened thousands upon thousands of cord blood samples to find the genetic abnormality before the New York patient was accepted for haplo-cord treatment.
The transplant was very successful for the woman. Since her transplant, she has been free from leukemia for over four years. She and her HIV specialists stopped her treatment three years after her transplant. She has not experienced a recurrence of the virus 14 months later.
Multiple ultrasensitive tests could not detect any signs in the woman's immuno cells of HIV capable of reproducing, nor any HIV antibodies. In a laboratory experiment, they also tried to infect the woman with HIV by drawing immune cells from her.
Dr. Bryson stated Tuesday that it would have been difficult to find a match and a rare mutation without cord blood cells. This opens up the possibility of a wider range of populations.
Bryson and her coworkers consider this woman to be in HIV remission at this point.
Bryson stated that it was not a good idea to call it "cure", and suggested that "remission" is better than "cure" in this stage.
This is a case in point: Deborah Persaud, Johns Hopkins, was the first to present a case study of a child from Mississippi in 2013. Persaud described a case of a baby who had contracted HIV from her mother. The child was given an unusually intense antiretroviral regimen soon after she was born. Persaud revealed that the toddler had been free from HIV treatment for 10 years without any viral rebound. The news of the supposed HIV cure spread quickly across the globe, sparking a media frenzy. However, the child's virus ended up rebounding 27-months after her treatment was stopped.
The authors of the case study in New York would consider the patient cured if enough time passes without the presence of any active virus. This could take a few years.
Bryson stated, "I'm thrilled that it's worked out so well for her." She said that the apparent success of the case has given researchers more hope and provided them with more options for the future.
Why are HIV and AIDS so hard to treat?
Dr. David Ho was one of the pioneers of combination antiretroviral therapy for HIV in 1996. He is also the director of Aaron Diamond AIDS Research Center in New York City. once famously stated that if given enough time, these medications could eradicate the virus.
There are only a few cases to date of HIV-positive people who were treated immediately after contracting the virus. They then stopped treatment and have been in HIV remission for many years.
Ho's prediction was wrong. HIV-cure researchers learned more and more about the difficult task of finding effective curative treatments that are safe, affordable, and scaleable over the past quarter century.
HIV is a constant presence in the body. This happens because the virus quickly splices into long-lived immune cell lines that enter a resting status. They stop producing new viruses. HIV is not susceptible to antiretrovirals as they only target replicating cells. This means that HIV can be left untreated in resting cells for long periods of time, sometimes even years. These cells can restart their engines and repopulate your body with large amounts of virus if there is no treatment for HIV.
Timothy Brown's case published in 2009 ignited HIV-cure research, which has seen an explosion of financial investment.
Two new cases of HIV remission were announced by researchers in 2019. These cases were following treatments similar to what Brown received . They included London resident Adam Castillejo who had Hodgkin lymphoma and a German man from Dusseldorf who had AML.
These two men have been HIV-free for more than three years. There has been no viral rebound. NBC News was informed by the authors of each case study -- Ravindra K. Gupta, University of Cambridge, and Dr. Bjorn J. Jensen of Dusseldorf University Hospital - that their patient had been "almost certainly" cured.
Two cases have been reported by scientists since 2020 that their own immune system has apparently cured them HIV. These two women are part of the 1 in 200 HIV-positive people known as elite controllers, whose immune systems can suppress viral replication without medication. Their bodies were able to stop viral replication even further, and reportedly destroyed every functional virus.
Less toxic treatment
The New York patient who received a haplo-cord transplant had another advantage. It was significantly less risky than the treatment she received for her three male predecessors. This is when the donor cells fight for the body of the recipient. This was the same for Brown and all three HIV-cure patients.
Brown, 54, died in September 2020 of recurrent leukemia.
In the hopes of curing HIV, the New York patient was the second to be transplanted with a haplocord. The first patient died from his cancer shortly after his 2013 treatment.
Bryson stated that the New York patient is "asymptomatic but healthy"
Bryson stated, "She's enjoying life."