In the history of HIV/AIDS, only a single person is believed to have been cured of the virus. Timothy Ray Brown, an American known as the “Berlin patient,” had HIV for more than a decade, until two stem-cell transplants in 2007 and 2008 cleared it from his body.
Now, according to a paper published in Nature on Tuesday, there might finally be a second such patient.
Like Brown, the new patient had cancer and received a cancer treatment involving chemotherapy to wipe out his immune system and replace it, via a stem-cell transplant, with non-malignant donor cells. In both cases, the donor cells also carried an added benefit: a genetic mutation that leads to HIV immunity.
In September 2017, sixteen months after the the May 2016 transplant in London, the patient — a man who prefers to remain anonymous — went off his antiretroviral drugs for HIV, yet still tested negative for the virus. So far, he’s remained HIV-free.
Since Brown, doctors have tried the same procedure in a handful of other HIV patients but, to date, the treatments didn’t work or the patients died from their cancer or complications of the transplant. It was never clear there’d be another success like Brown’s.
“By repeating the procedure in another patient,” said Gero Hütter, the German hematologist who treated Timothy Ray Brown, “there is more evidence that the ‘Berlin patient’ is not a sole exception.”
In the three-and-a-half decades since HIV was discovered and began spreading around the world, killing 35 million people, doctors and researchers have made remarkable progress against the virus. They figured out how to get people tested and diagnosed quickly, and uncovered effective treatments that allow those with HIV to live long, relatively healthy lives. Public health officials also waged awareness campaigns about prevention, reminding people to practice safe sex with condoms and get tested, and that early HIV treatment can save lives.
But an HIV cure has remained elusive. And the history of the virus is littered with cases where patients’ infections were reversed only to come back months later.
That’s why Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, advised caution around the new study results. “We really need to wait longer to see if this really is the second ‘cure.’”
But other experts were less circumspect, calling the London patient “cured” in interviews, though doctors haven’t yet agreed on what an HIV cure means, Hütter said, since there has only been one other patient cleared of the virus. For now, the study offers a glimmer of hope — that a cure could be within reach, and that new approaches to treating HIV may be effective.
The Berlin patient: how doctors used a stem cell transplant to clear HIV
To understand the Nature paper’s London patient, we need to step back and understand what happened with the Berlin patient, Timothy Ray Brown, the only person believed to be cured of HIV.
An American living in Berlin, Brown found out he had leukemia in 2006, eleven years after an unrelated diagnosis of HIV. Like many people living with HIV today, Brown used antiretroviral treatments to suppress the virus to the point that it was undetectable.
But his cancer wasn’t as easy to manage. For treatment, Brown was referred to Charité Medical University in Berlin, and to a blood-cancer doctor, Gero Hütter. Because Brown’s leukemia had stopped responding to chemotherapy, Hütter recommended an allogenic stem cell transplant as the next step.
Leukemia is a blood and bone marrow cancer, and “allogenic” transplants involve wiping out the immune system with chemotherapy and replacing it with donor hematopoietic stem cells. These cells are typically found in the bone marrow, and they produce blood and immune system cells. The idea is that the new cells from a cancer-free donor will regenerate the recipient’s immune system, clearing the patient of malignant cells.
Instead of just looking for a donor who was a tissue match, though, Hütter had a novel idea: to seek out someone who also carried a CCR5 delta 32 mutation.
CCR5 is a protein receptor on the surface of immune cells that the HIV virus uses as its entry point into the immune system. One percent of people of Northern European origin are born with no CCR5 receptor on their immune cells, having inherited two copies of the mutated gene from both of their parents. These people are carriers of a “homozygous” CCR5 delta 32 mutation, which renders them resistant to HIV.
According to a report in New York Magazine, Hütter was surprised that no other doctor had ever tried this approach to HIV treatment before and convinced the staff at the donor registry in Germany to test all of Brown’s potential donor matches for the mutation. By donor 61, they found the perfect candidate: a tissue match who was also a homozygous carrier of the mutated gene.
In 2007 and 2008, Brown received two bone-marrow stem-cell transplants for his leukemia from the donor. In 2008, Hütter reported on the preliminary results, suggesting his hunch was correct: though Brown was no longer taking antiretroviral medications, he appeared to be HIV free. Hütter published the final results in the New England Journal of Medicine a year later.
More than a decade on, Brown, who is 52 and now lives in Palm Springs, California, remains clear of the virus.
Why the London patient is important
Since that experiment, other doctors have not been able to repeat Brown’s success. Of the dozen patients with HIV who have gotten a transplant like Brown’s — involving CCR5 delta 32 homozygous donor cells — eight died from transplant-related side effects or cancer relapses, Hütter told me. The rest are in remission but still taking antiretroviral treatments. So it’s not yet clear whether they’d be free of the virus without the drugs.
“The problem is that we have no long term followup data in these other patients,” Hütter said. That’s why doctors haven’t known whether Brown is an anomaly.
That’s also why the London patient is special: he’s the first person since Brown who survived a transplant, went off HIV treatment, and remained HIV-free for more than a year.
The London patient was diagnosed with HIV in 2003, and advanced Hodgkin’s lymphoma, a cancer of the lymphatic system, in 2012. He wasn’t responding to chemotherapy. Like leukemia (and a growing list of other diseases), some forms of lymphoma can be treated with stem-cell transplants, and doctors recommended he try one from a donor who also carried the CCR5 mutation.
The patient got the transplant in London in May 2016. The study, led by researchers at UCL and Imperial College London, did not disclose the name of the institution where the procedure took place. But the experience is already helping scientists answer important questions about stem-cell transplants for HIV.
Is this the second “cure”?
“After the ‘Berlin patient’ there was a controversy [about] which part of the treatment was responsible for the cure from HIV,” Hütter explained. “Was it the transplantation procedure, was it the CCR5 [mutation in the donor cells], was it immune reaction or was there something special, unique in the patient?”
The new study offers a clue. Both the London patient and the Berlin patient received the homozygous CCR5 cells. But there were several differences between the two cases. The Berlin patient had two transplants and radiation as well as chemotherapy, which caused severe side effects and nearly killed him. The London patient got one transplant and a much milder chemo regimen, suggesting that an extremely toxic chemo and radiation treatment isn’t required for the procedure to work.
But again, it’s still early days. The study authors referred to the London patient as being in a “sustained remission”, saying it would be premature to call him “cured.” It’s still possible that the patient’s HIV could rebound, though Hütter believes that’s unlikely: the other patients who saw the virus return following a transplant did so within one year.
Maybe even more importantly, like the Berlin patient, this person also had a type of HIV — known as a CCR5 dominant HIV strain — that might be more receptive to a transplant with the CCR5 cells, since this HIV type uses CCR5 receptors to infect people. “It’s possible [the transplant] only works with this CCR5 dominant strain but we have not proved it yet,” Hütter added.
Both patients also had “graft versus host disease,” a transplant complication when the donor’s stem cells attack the recipient’s. That could turn out to be an important part of the treatment response.
Regardless of how the treatment worked, it’s probably not a realistic approach for everybody with HIV. The chemo that comes with stem-cell transplants is still toxic, and knocking out a person’s immune system can be deadly — and extremely expensive.
But the study’s lead author, Ravindra Gupta of UCL (who did not respond to Vox’s request for comment), said in a press release that he hopes this line of research might lead doctors to figure out other methods for rejiggering the immune system to resist HIV, so that patients don’t need risky transplants. The London patient might very well be the second step in that direction.