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 the 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 perk: 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. To date, he’s remained HIV-free.
Since Brown, doctors have tried the procedure in a handful of other cancer patients but most of them died because of their cancer, side effects of the transplant, or saw a return of the virus after quitting antiretroviral drugs. It was never clear whether 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 nearly 40 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.
In the US, there are more than a million Americans living with HIV, and about 40,000 new infections are diagnosed here every year — an indication that health officials still struggle to prevent the virus from spreading.
But an HIV cure has remained elusive. And history of the virus is littered with cases where patients’ infections were reversed only to come roaring 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 (even though doctors haven’t yet agreed on what an HIV cure means, Hütter told Vox, since there has only been one other patient cleared of the virus.) For now, the study offers a glimmer of hope — that a cure may be within reach, and that new approaches to HIV treatment could be effective. Here’s why.
The Berlin patient: how doctors used a stem cell transplant to clear HIV
To understand the Nature paper, 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 radiation. The immune system is the replaced with donor hematopoietic stem cells, typically found in the bone marrow, which produce blood and immune system cells and can regenerate the immune system. The idea is that the new cells from a cancer-free donor will clear the patient of malignant cells.
Instead of just looking for a donor who was a tissue match, though, Hütter had a new idea: to seek out someone who also carried a CCR5 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 patients (known as a “homozygous” mutation). This renders them resistant to HIV.
According to a report in New York Magazine, Hütter was surprised that no other doctor had ever tried this 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.
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.
The London patient’s story
Since that experiment, other doctors have not been able to repeat Brown’s success. Of the patients with HIV who have gotten transplants like Brown’s, Hütter told me, most died from transplant-related side effects or cancer relapses. A minority 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 could never be sure that Brown was not an anomaly.
But the London patient is different: the first longer term followup of a person 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.) And his experience is already helping scientists answer important questions about stem-cell transplants for HIV.
Is the London patient 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 homozygous CCR5 cells, meaning the donor carried two copies of the gene. 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 milder chemo only, suggesting that an extremely toxic combination of chemo and radiation 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 transplant with CCR5 mutation cells, since it uses CCR5 receptors to enter the cells. “It’s possible [the transplant] only works with this CCR5 dominant strain but we have not proved it yet,” Hütter added.
Even if it did work for different HIV types, the chemo that comes with stem-cell transplants remains toxic, and knocking out a person’s immune system can be deadly — so it’s not a realistic treatment option for everybody with HIV.
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 help doctors figure out how to do that.