- A 66-year-old man who was living with HIV and leukemia is now in remission from both the virus and blood cancer following a successful stem cell transplant from a donor who possesses an extremely rare genetic mutation.
- He is the fourth person in the world to achieve long-term remission of HIV.
- While his case and course of treatment are very specific to individuals living with the virus and blood cancers, researchers say it’s an important development in the treatment of HIV.
In July, cancer research and treatment center City of Hope presented research at the 2022 International AIDS Conference that shed a positive spotlight on the continued push to better understand, treat, and combat HIV.
The news reverberated around the world — the 66-year-old patient, who wishes to remain anonymous, is the oldest individual to achieve remission from both HIV and leukemia, following a successful stem cell transplant from a donor who possesses an extremely rare genetic mutation.
He is just the fourth person in the world to achieve long-term remission of HIV. While his case and course of treatment are very specific to individuals living with the virus and blood cancers, researchers say it’s an important development in the long winding road to better tackling HIV.
In the course of this man’s adult life, he has seen quite an evolution, from his initial diagnosis of HIV in 1988 at the height of the global AIDS crisis, to today, being in remission for over a year.
The case of the ‘City of Hope patient’
“The most significant finding from this study was the outcome. ‘The City of Hope patient’ achieved dual long-term remission from HIV and acute leukemia after his stem cell transplant using stem cells from a donor who carries the homozygous CCR5 delta 32 mutation, and his experience is unique from his predecessors,” said Dr. Jana K. Dickter, City of Hope associate clinical professor in the Division of Infectious Diseases, who presented the data on the patient at the international conference.
“He is the oldest person to receive a stem cell transplant and go on to achieve dual remission,” she added.
Dickter told Healthline this man especially stands out from his predecessors given he lived the longest with HIV at the time of his stem cell transplant and received the “least immunosuppressive regimen” prior to transplantation.
“The results of this research are profound for people living with HIV and blood cancers for a few reasons. As people continue to live longer with HIV thanks to antiretroviral therapy, they are also at an increased risk of developing blood cancers and stem cell transplantation may be a good option for them to treat their cancer,” she explained. “We now have evidence that some HIV patients with blood cancer may not need as intensive immunosuppressive therapies prior to transplant to put them in remission for their HIV.”
Dickter added that this case shows if clinicians can find the correct stem cell donor, they can “potentially use newer, more advanced and less intense chemotherapy regimen options that are better tolerated for older patients” in addition to the hope that there is potential for dual remission from both diseases for these specific patients.
The research on this man’s specific case was presented on July 27 at the conference and revealed that this man received his transplant nearly three and a half years ago at City of Hope, according to a press release.
His case required a very specific stem cell transplant.
He was living with acute myelogenous leukemia, a type of the disease that appears more often in people living with HIV later in life. The rare genetic mutation — homozygous CCR5 delta 32 mutation — found in the volunteer donor actually makes those who have it resistant to most strains of HIV infection.
CCR5 serves as a receptor on CD4+ immune cells, and attracts HIV as a potential entryway to hit a person’s immune system. What happens is the mutation actually puts up a roadblock to that entry point, preventing HIV from replicating, the release reads.
Finding the right donor for someone like this patient can be marked by an exhaustive search, and from there, the stem cell transplant itself can be an arduous process that can result in serious health complications.
This man received three different therapies to get him to achieve remission from his leukemia before receiving his transplant. For comparison, most people in his position achieve remission after a sole therapy.
The genetic mutation needed for a donor match for this particular patient is found in only 1 to 2% of the population at large. The procedure was a success, and City of Hope revealed that he did not show signs of serious medical issues after the transplant.
Dr. Joseph Alvarnas, professor, Department of Hematology & Hematopoietic Cell Transplant and vice president for government affairs at City of Hope, told Healthline that immense research and work goes behind making these kinds of stem cell matches between donor and patient.
After ruling out direct relatives who might be a match, researchers turn to Be the Match, which collaborates with registries globally. It is touted as the world’s largest and most diverse registry of potential blood marrow donors, reaching 25 million potential donors, as of a 2015 announcement.
Alvarnas said that this case underscores how important it is to do targeted donor searches for this kind of mutation.
“The patient that we are discussing is really important, because as we go to screen patients in the future, this idea that we will also be seeking a donor with the CCR5 delta 32 mutation, for instance,” he said. “It should become more a part of what we do on a routine basis.”
When it comes to this man, Alvarnas said he developed myelodysplastic syndrome, what he called a “pre-leukemia, a change in the blood, a malignancy that over time can evolve toward acute leukemia.”
“That particular illness is not curable without a blood and marrow transplant from a donor. For this individual it is a disease that is even higher risk, meaning they not only started with myelodysplastic syndrome but developed leukemia. That leukemia was pretty tough to treat in that it took three different lines of leukemia therapy to help get him into remission sufficient enough to be able to undergo transplantation,” Alvarnas explained.
“For patients like these, we always worry about the specter of whether or not the leukemia can be potentially resistant to the combined effects of the medicine they get prior to the transplant as well as the immunological effects of the donor’s immune system upon the leukemia, which is what we mean by a risk of relapse.”
“So, for this person, miracle number one is being cured of a life threatening disease — that’s the leukemia derived from myelodysplastic syndrome,” he added. “The other amazing thing is the fact that in the context of delivering life-saving care, you can add another level of transformational value to that person’s life.”
What this means for others living with HIV
The news about the “City of Hope patient” comes on the heels of news earlier this year of the first woman who might have achieved remission of HIV from stem cell transplants.
These stories are significant for these individuals themselves but also “serve as a ‘proof of concept’ in terms of the HIV cure agenda,” explained Dr. Monica Gandhi, MPH, Professor of Medicine and Associate Division Chief (Clinical Operations/ Education) of the Division of HIV, Infectious Diseases, and Global Medicine at UCSF/ San Francisco General Hospital.
“Humans require both the CD4 cell receptor and a co-receptor called CCR5 to take in the virus and become HIV-infected. Those born without a CCR5 receptor — about 10 percent of the population in some places in Europe, likely evolved due to smallpox protection in the past — cannot be infected with HIV,” Gandhi wrote in an email to Healthline. “This handful of individuals, including this new remission case at the City of Hope medical center, received a stem or bone marrow transplant for leukemia or lymphoma from someone who did not have the CCR5 receptor (after their own immune system wiped [it] out from chemotherapy), making their new cells unable to take in HIV and, thereby, achieving cure.”
Gandhi, who was not affiliated with this research, said it will be interesting to see if, down the line, there are “less invasive ways to work with the CCR5 receptor to achieve ‘cure’” that would not be as dangerous as a stem cell transplant, for example.
Gandhi, Alvarnas, and Dickter all stressed that one needs to contextualize headlines about these cases that casually throw around the word “cure.”
These four cases so far specifically apply to people living with HIV with blood cell cancers and do not apply to the population of people living with HIV at large.
When asked about ramifications of this case, Gandhi said doctors who treat “any patient with a blood cancer and HIV should strive to find a match during the stem cell or bone marrow transplant process of cells from a donor who does not carry the CCR5 receptor on their surface.”
Gandhi said these matches are very difficult to achieve during the donation process. First and foremost, their cancer should be treated “as soon as possible at all costs,” she wrote.
“When a donor match can be achieved with this criteria, the patient living with HIV does have a chance to achieve long-term remission like in this case,” Gandhi added.
When asked if this man’s HIV could return to detectable levels Dickter said that there currently is no evidence of HIV replicating in his system.
“We don’t use the term ‘cure’ lightly. This is because HIV can hide in reservoirs in the body, so the term ‘cure’ implies there is complete eradication of the virus from the body. We can’t find any of it — we looked in places in his blood, looked at tissues in the gastrointestinal tract — as of right now, we can’t find any evidence of replicating HIV despite [him] being off antiretroviral therapy,” Dickter said. “But, before we commit to using the term ‘cure,’ it takes more time and more data. However, what we are seeing now is quite promising.”
She added that they are continuing to monitor his health and the presence (or lack thereof) of active HIV.
“There is a possibility that all of the patient’s original CD4 containing cells may not have been destroyed during the preparation for the stem cell transplant, so they could eventually create a cell line able to accept HIV so that the patient’s cells will be seeded with HIV again,” Gandhi wrote of whether HIV could once again be found to be detectable in this man’s system.
“However, this is unlikely given the length of time the patient has had off of antiretroviral therapy without a relapse of HIV and examples from the few other cases we have. But, yes, there is always a possibility and this patient should receive regular HIV viral load testing throughout his life to ensure he stays in remission off of antiretroviral therapy.”
Putting this in context: From the beginning of the HIV crisis to today
To put it very mildly, this man has witnessed — and intimately lived through — immense change when it comes to the state of the HIV crisis and what it means to live with it.
Gandhi wrote that this man “is a model in two ways.”
“First, his case demonstrates the power of antiretroviral therapy, which has kept him alive and living a normal life since he was placed on such therapy (with the more highly active antiretroviral therapies being available in 1996). So, that is exemplary that he has done so well for so long on powerful HIV therapies,” she wrote.
“The second model, in this case, is that the patient was able to achieve long-term remission from HIV after suffering from leukemia showing the tantalizing power of a potential cure for others in his position and, in the future, even for those who do not have blood cancer,” Gandhi added.
For Dickter, the outcome of this case is profound. When he was first diagnosed with HIV in the late 1980s, he actually had AIDS.
“He had seen many of his friends and loved ones get very sick and ultimately die from the disease. He also experienced quite a bit of stigma at the time. Fortunately, he was able to get on antiretroviral therapy by the late ’90s and he was doing really quite well until he was diagnosed with leukemia,” Dickter said. “Fortunately, City of Hope was able to perform this stem cell transplant, which led him to go into remission from the acute leukemia and HIV simultaneously and it’s just been a remarkable experience for him and for us, actually.”
This man’s story offers a glimpse of other hopeful outcomes.
“As an infectious disease doctor, I always hope that someday [I can] tell patients there is no remaining evidence of the virus in their system,” she said. “And we were able to do that with this patient who has been living with HIV for three decades.”