A handful of people with HIV have been cured after receiving HIV-resistant stem cells – but a man who received non-resistant stem cells has become the seventh person to be left HIV-free after receiving a stem cell transplant to treat blood cancer, reports New Scientist.
Significantly, he is also the second of the seven who received stem cells that were not actually resistant to the virus, strengthening the case that HIV-resistant cells may not be necessary for an HIV cure.
“Seeing that a cure is possible without this resistance gives us more options for curing HIV,” said Christian Gaebler at the Free University of Berlin.
Five people have previously become free of HIV after receiving stem cells from donors who carried a mutation in both copies of a gene encoding a protein called CCR5, which HIV uses to infect immune cells. This led scientists to conclude that having two copies of the mutation, which completely removes CCR5 from immune cells, was crucial for curing HIV.
“The belief was that using these HIV-resistant stem cells was essential,” said Gaebler.
But last year a sixth person – known as the “Geneva patient” – was declared free of the virus for more than two years after receiving stem cells without the CCR5 mutation, suggesting CCR5 isn’t the whole story – although many scientists think the roughly two-year virus-free period isn’t quite long enough to show they were actually cured, said Gaebler.
The latest case strengthens the idea that the Geneva patient has been cured.
It involves a man who, in October 2015, received stem cells to treat leukaemia, in which immune cells grow uncontrollably.
The man, 51 at the time, had HIV. During his treatment, he was given chemotherapy to destroy the vast majority of his immune cells, making room for the donor stem cells to produce a healthy immune system.
Ideally, he would have received HIV-resistant stem cells, but these weren’t available, so doctors used cells that carried one typical and one mutated copy of the CCR5 gene. At the time, the man was taking a standard antiretroviral therapy.
But about three years after the transplant, he chose to stop taking ART. “He felt he’d waited some time after the stem cell transplant, he was in remission for the cancer, and he was always feeling that the transplant would work,” said Gaebler.
Shortly after, the team found no signs of the virus in his blood samples. He has since remained free of the virus for seven years and three months, enough for him to be considered “cured”.
He has had no detectable HIV in his body for the second longest period of the seven people declared free of the virus – with the longest case being HIV-free for about 12 years.
“It’s amazing that 10 years ago his chances of dying of cancer were extremely high and now he’s overcome this deadly diagnosis, a persistent viral infection and he’s not taking any medications – he’s healthy,” said Gaebler.
The discovery upends our understanding of what’s required for curing HIV via this approach. “We thought you needed to transplant from donors that lack CCR5 – it turns out that you don’t,” said Ravindra Gupta at the University of Cambridge, who wasn’t involved in the study.
No replication
Scientists have generally thought that such cures relied on any virus lurking in the recipient’s remaining immune cells, after chemotherapy, being unable to infect the donor cells, meaning it can’t replicate. “Essentially, the pool of host cells to infect runs dry,” said Gaebler.
But the latest case suggests that instead, cures can be achieved as long as non-resistant donor cells are able to destroy any of the patient’s remaining original immune cells before the virus can spread to them, speculates Gaebler.
Such immune reactions are often driven by differences in the proteins displayed on the two sets of cells. These make the donor cells recognise residual recipient cells as a threat to eliminate, he added.
The findings suggest that a wider pool of stem cell transplants than we thought, including those without two copies of the CCR5 mutation, could potentially cure HIV, said Gaebler.
But it is likely that many factors, like the recipient’s and donor’s genetics, need to align for this to work, so that, for instance, the donor’s cells can rapidly destroy the recipient’s. What’s more, in the latest case, the man carried one copy of the CCR5 mutation, which could have altered how his immune cells were spread across the body in a way that made it easier to cure him of the virus, said Gaebler.
This means that most people receiving stem cell transplants for HIV and blood cancer should be offered HIV-resistant stem cells where possible, said Gaebler.
It’s also important to point out that cancer-free people with HIV won’t benefit from stem cell transplants, as it’s a very risky procedure that can lead to life-threatening infections, noted Gaebler. Most people are better off taking ART, which is a much safer and convenient way to stop HIV from spreading.
Nonetheless, efforts are being made to cure HIV by genetically editing immune cells, and prevent it using vaccines.
Promising path to HIV cure
Meanwhile, in the United States, a small, highly anticipated study shows another glimmer of hope in the long effort to control HIV without medication and search for a cure for a virus that attacks immune cells, reports The Washington Post.
Researchers gave 10 people with HIV a complex regimen of experimental immunotherapies, then discontinued the daily pills that kept the virus at bay. In six of them, the virus rebounded slowly and stayed at a low level for months, and one person’s immune system kept the virus in check for more than a year and a half – giving scientists hope that they could optimise the approach to create a cure.
“It’s provocative, but I’ve been doing treatment interruption studies for 30 years, and this is unexpected and unparalleled,” said Steven Deeks, a Professor of Medicine at the University of California-San Francisco (UCSF) and one of the leaders of the study.
He and other scientists were quick to caution that this is a promising step forward, not a solution. The small study did not include a control group, so more studies will be needed to confirm and flesh out the exciting signal.
“I am very excited about the findings. The study, although small, will drive new directions in the field,” said Sharon Lewin, director of the Doherty Institute at the University of Melbourne. “This is something the field urgently needs.”
More than 40m people are estimated to be HIV+ worldwide, according to the World Health Organisation. And while antiretroviral drugs have been transformative, a cure is a long-sought goal.
Tom Perrault (60), had been taking a daily pill since 2005. He participated in the UCSF trial and, after receiving a “kitchen sink” of immunotherapies, stopped taking his daily medication in early July 2021.
“It didn’t come back in July, didn’t come back in August, didn’t come back in September, didn’t come back in October,” Perrault recalled. “All of a sudden, I thought: ‘My body is suppressing it. I think it’s working. This is exceeding their expectations’.”
But in November he got a call from doctors at UCSF. His heart sank. The virus had rebounded. Despite the setback, he said the study was a revelation.
“I was surprised by the level of emotion,” Perrault said. “All of a sudden, I dared hope. You want to hope. What a gift this will be for the world if and when this would work.”
The latest study was published in Nature, along with the Berlin case.
Since 2009, when the first “Berlin patient” was apparently cured of HIV after a transplant to treat leukaemia (he died in 2020 after a leukaemia relapse), these cases have seized the world’s attention because they show what is possible.
But bone marrow transplants are risky procedures, and a cure depends on donors who carry a rare mutation that blocks the virus’ ability to enter immune cells.
Yet another paper focuses on untangling the biological reason that some people who have HIV, and take an experimental treatment that targets the virus, are able to control the virus long-term, without additional medication.
The trial led by Deeks was an intensive experiment, requiring about 60 clinic visits over two years, and the co-operation of multiple research groups and pharmaceutical companies. It pooled together three immunotherapy approaches – drugs that ignite and shape a person’s immune response.
“This has been a long-anticipated study, and it has kept the field watching closely,” said Javier Martinez-Picado, a Research Professor at IrsiCaixa, an HIV research institute based in Barcelona.
He said the results were exciting and highly promising, because they are a proof of concept that can increase scientists’ understanding of what allows some people to control the virus after treatment is stopped.
Antibodies
First, people received an experimental vaccine aimed at triggering immune cells called T cells to fight the virus in their bodies. Then, they received two broadly neutralising antibodies – which target HIV and have been tested also for HIV prevention – plus a drug to activate the immune system.
Then, they received another round of antibodies, and stopped taking daily pills to keep the virus in check.
The approach was tested in a monkey study that showed the majority of animals controlled the simian version of HIV.
“The idea is that if you increase immunologic control of virus, then you might be able to prevent or slow viral rebound after you stop antiretroviral therapy,” said Dan Barouch, director of the Centre for Virology and Vaccine Research at Beth Israel Deaconess Medical Centre.
He led the primate study, but his lab is also running a clinical trial testing combinations of immunotherapy in people, and expects to report results next year.
Barouch noted that because of the lack of control group, it was not conclusive that the rebound was slower in the six people in the San Francisco study. However, he said what was most intriguing was that the researchers found that those patients who appeared to partially control the virus had an early response in a specific population of T cells.
“They were ready to pounce on the virus as it was coming out,” said Rachel Rutishauser, an immunologist and infectious-disease doctor at UCSF and a leader of the study.
“We’re not advocating that this is the therapeutic regimen to take into the clinic. … We can start to learn and how can we make the T cells better.”
Nature study – Sustained HIV-1 remission after heterozygous CCR5Δ32 stem cell transplantation
New Scientist – Man unexpectedly cured of HIV after stem cell transplant (Open access)
The Washington Post article – Small study shows a promising path toward HIV cure (Restricted access)
See more from MedicalBrief archives:
‘Berlin Patient’ patient speaks in Cape Town on HIV cure research
‘Geneva’ HIV patient possibly cured in new case
Man declared ‘HIV-free’ after stem cell transplant