Photo by Robert Hood / Fred Hutch News Service
Seattle-born Timothy Ray Brown was once known as the “Berlin Patient” because that is where he lived when he became the first person in the world to be cured of HIV.
On Monday, after 12 long years, there is now a “London Patient,” only the second person likely cured of HIV, the virus that causes AIDS — and word about it came Monday at a scientific conference in Seattle.
The report by British and other European authors about this second patient was also released in the scientific journal Nature.
Both of these HIV-positive men were struggling with a lethal blood cancer, and both were saved from that cancer by transplants of blood stem cells. They both were apparently cured of HIV because the donors of those stem cells each carried rare genes that confer natural resistance to the virus.
Because the transplant wiped out his HIV, Brown’s case made world headlines when the “Berlin Patient’s” story was first revealed in the New England Journal of Medicine in 2009. It has taken so long to repeat this cure that Brown’s case began to look like a fluke, but now it has happened again, and the headlines are back.
Photo by Robert Hood / Fred Hutch News Service
“This is very exciting,” said Dr. Hans-Peter Kiem, director of the Stem Cell and Gene Therapy Program at Seattle’s Fred Hutchinson Cancer Research Center, where bone marrow transplants to cure cancer were pioneered 40 years ago. Holder of the Stephanus Family Endowed Chair for Cell and Gene Therapy, Kiem is a world leader in efforts to genetically engineer HIV resistance into blood cells as a potential cure for HIV.
“I think this supports our thinking that this kind of stem cell transplant can cure HIV,” he said. “Now we just need to make it more tolerable for patients without cancer and better understand the mechanisms involved.”
Kiem and other scientists stress that there is no certainty that the unnamed man treated at a London hospital will remain HIV-free. In their Nature report, the doctors involved cautiously state that because the patient stopped taking antiviral drugs for only 18 months, it is “premature to conclude” he has been cured.
Yet signs do point to a second cure. Typically, when antiviral drugs are stopped in any patient with no detectable virus, HIV returns from hidden reservoirs within the body to high levels in blood within just a few weeks.
The Berlin Patient’s advice to the London Patient
Brown, 52, now lives in Palm Springs, California. But he was in Seattle on Sunday to attend a workshop hosted by defeatHIV, a research group based at Fred Hutch that is working on ways to develop a cure for HIV. The public-private partnership, which receives funding from the National Institutes of Health and is co-directed by Kiem and colleague Dr. Keith Jerome, was inspired by Brown’s transplant, which proved for the first time that a cure was possible.
Brown has worked closely with defeatHIV and Fred Hutch in recent years. As has become a tradition, the all-day workshop ended Sunday with a ceremonial birthday cake to celebrate Brown’s 12th anniversary of being HIV-free, and he blew out the candle with gusto.
Not surprisingly, Brown said he hoped one day to meet the London Patient, whose name he does not know. They will have a lot of notes to compare.
“I would say this guy should take his time to come out,” he advised. “I took a couple of years before I decided to go public, and I’m glad I did. It was an important decision. When he is ready to reveal who he is, he can do that. And if not, I completely understand.”
Brown protected his privacy for two years after his successful treatment in Germany, but on his return to the United States he revealed in 2010 that he was the “Berlin Patient” because he wanted to help raise awareness of the possibility of a cure.
How the ‘London Patient’ was likely cured of HIV
Release of the report was set to coincide with a presentation about the London Patient’s case at the Conference on Retroviruses and Opportunistic Infections, or CROI, the world’s premier annual scientific conference that tracks developments in HIV/AIDS research, now underway in Seattle. But the place had been buzzing with rumors of a second Timothy Ray Brown case, and the story leaked.
As described by the Nature paper’s lead authors, Drs. Ravindra Gupta of University College London and Eduardo Olavarria of Imperial College London, their transplant patient experienced quite similar treatment to Brown’s, with some notable differences.
Brown was HIV positive and desperately ill with acute myeloid leukemia when he had the first of two transplants; the second required 20 months of waiting after the first because the leukemia, not the HIV, came back. The London Patient received a single blood stem cell transplant for Hodgkin lymphoma. Both are serious, life-threatening blood cancers.
While transplantation is a risky procedure that is difficult for many patients to endure, the London Patient recovered quickly, whereas Brown’s two transplants were a brutal ordeal that nearly killed him. Transplant requires a procedure called conditioning, which involves intense chemotherapy and sometimes radiation to destroy the diseased immune cells, many lodged in the bone marrow and gut. Brown received both radiation and intensive chemotherapy. The London Patient received a much milder regimen of chemotherapy drugs. That is an important distinction, because it hints that it is not necessary to use a “sledgehammer” of intensive radiation to eliminate HIV reservoirs.
Photo by Robert Hood / Fred Hutch News Service
Hutch virologist and defeatHIV Co-Director Jerome said the goal of cure researchers is to go even gentler. “Our long-term goal is to develop a simple and inexpensive version of this cure, which can be offered to everyone living with HIV, regardless of where they are in the world,” he said.
Brown stopped taking antiviral drugs at the time of this first transplant; the London Patient stayed on his anti-HIV medications throughout the first 17 months of his transplant recovery. He stopped them only 18 months ago.
Both patients received blood stem cells from donors who carried HIV-resistant genes. The so-called CCR5 mutation deletes part of a protein on the surface of blood cells that HIV uses like a mechanical gate to pry its way in and infect the cell. About 1 percent of people of northern European ancestry carry that mutation from both their mothers and fathers. Another 10 percent of people from those northern climes carry at least one of those genes.
The donors for both Brown and the London Patient carried two copies of that mutation, one from the mother and one from the father, a “homozygous” trait that makes them virtually immune to HIV infection.
Transplant as an HIV cure: many attempts, few successes
As the Nature authors noted, the apparent cure of a second patient shows that Brown’s success “was not an anomaly.” Yet the news is tempered by the fact that it took doctors 12 years to repeat his favorable result.
One reason it has taken so long, Jerome said, is that it is difficult to find that 1 percent of donors who carry both copies of the rare gene. HIV-positive patients who require a transplant to survive cancer are also unfortunately rare, because they are often too sick to qualify for the difficult procedure.
Dr. Carl Dieffenbach, who heads AIDS research for the National Institues of Health and who was in Seattle for CROI, said that experiments like these — which put patients at great risk — are still appropriate because the people involved are so desperately ill.
“These therapies are used in situations where the life of the patient is on the line,” he said. “It is important to remember there have been a significant number of attempts to achieve this, and many other cases resulted in the death of the patient from their cancers. That just points to the difficulty.”
Dr. Monique Nijhuis of the University Medical Center of Utrecht, the Netherlands, and a co-author of the Nature paper, described significant efforts in Europe to provide transplants to HIV-positive patients. Through a consortium, IciStem, doctors have amassed a registry of 22,000 potential transplant donors who carry HIV-resistant genes. The European group has also been tracking results from 39 HIV-positive blood stem cell transplant patients, 26 of whom are still living. The London Patient is one of those cases.
In the Nature paper, the authors said they know of only one other case of a patient who was transplanted and also interrupted his HIV treatment like Brown and the London Patient have done. That case involved a German known as the “Essen Patient,” and after stopping antivirals he experienced a rapid rebound of HIV.
In another closely watched set of cases, three HIV-positive patients from the Boston area received transplants of blood stem cells that did not carry the mutation. The idea was to see if the rigorous transplant procedure alone, rather than the mutant cell types, cleared HIV. In fact, the virus did not rebound quickly, but it eventually did, at 12, 32 and 41 weeks, respectively, for the three.
Sabin Russell is a staff writer at Fred Hutchinson Cancer Research Center. For two decades he covered medical science, global health and health care economics for the San Francisco Chronicle, and wrote extensively about infectious diseases, including HIV/AIDS. He was a Knight Science Journalism Fellow at MIT, and a freelance writer for the New York Times and Health Affairs. Reach him at email@example.com.
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