When Dr. Gero Hütter gave Timothy Ray Brown a bone marrow transplant at a Berlin hospital on Feb. 7, 2007, he knew he could be making history. If, that is, Brown survived long enough to see whether the grueling transplant cured not only his leukemia but also his infection with HIV, the virus that causes AIDS.
Brown did survive, and eight years later, is free of both cancer and HIV. On Thursday, the German doctor reunited with his Seattle-born patient for a rare joint public appearance to talk about how the world’s first -- and so far only -- HIV cure came about and what it means for the future.
“At the time we were doing the transplant, we knew we were doing something very special that could change the whole medical world if it worked,” Hütter told a standing-room-only crowd of more than 200 people - including Brown’s mother – at the downtown Seattle Public Library. “We weren’t clear what would happen. It was a big and good surprise that it worked.”
Added Brown: “I didn’t really believe I was cured until he published the paper [in the New England Journal of Medicine in 2009].”
Identified only as “the Berlin patient” in that first paper and in subsequent media reports, Brown, 48, went public in 2010, around the time he returned from Berlin to live in the United States.
“I decided I needed to tell my story so other people could get cured as well,” he said. “I decided I was going to be an activist for a cure for HIV.”
At Thursday’s talk and during a visit earlier in the day to Fred Hutchinson Cancer Research Center – which pioneered bone marrow transplants and is now home to a research consortium on curing HIV – Hütter talked about what it was like to be the doctor who brought about the cure.
An oncologist by training, Hütter, 45, is the first to admit that he didn’t know much about HIV. But like many doctors who came of age or trained in the 1980s or early 1990s – before antiretroviral therapy revolutionized AIDS treatment, for those who have access to and can tolerate the drugs – he was deeply affected by the epidemic.
“I was very scared of HIV when it came out in the ‘80s,” he said. “It was my time when my sexual activity started. I was scared of this thing. When I started medical school in 1992, there was no active treatment, and I saw people die.”
That was why a paper he read while in medical school made such an impression on him. It described a rare genetic mutation called the CCR5 delta-32 deletion, which confers natural resistance to HIV. The mutation prevents CD4 cells – infection-fighting white blood cells that HIV targets – from developing a receptor, called a CCR5, on their surfaces. HIV uses this receptor to enter the cell. Without it, it’s as though HIV is left standing at the door without a key to get in.
“I was so impressed as a student that I kept this information for 10 years in my mind,” Hütter said. “When Timothy came and I saw he had leukemia and HIV, it was clear to me that we had to find a donor who had this mutation.”
For his part, Brown wasn’t interested in “being a guinea pig,” he said. He was far more concerned about his new diagnosis – acute myeloid leukemia – than his old one. He had learned in 1995 that he was infected with HIV, but a year later, antiretroviral therapy was found to control it. So he hoped to be able to cure his cancer with chemotherapy rather than a riskier transplant. But when chemotherapy failed, he agreed to Hütter’s plan to try to cure both.
The transplant itself was no different from what any patient with leukemia would undergo except that it required an additional step beyond the already complex process of finding a tissue-type match between donor and patient: A matching donor also had to have two copies of the CCR5 mutation, one from each parent.
It helped that Germany, where Brown was living at the time, had a large, centralized registry of stem cell donors, and the CCR5 mutation is most common in northern Europeans. Testing for the mutation is fairly simple and cost only an additional $500, Hütter said. Brown had a high number of tissue-type matches – 232. The 61st one tested had both copies of the mutation.
Hütter turned to data from Fred Hutch, amassed from years of transplant research, to assure himself that stem cells with the mutation would not adversely affect the leukemia treatment. (On Thursday – his first actual visit to the Seattle campus – he said, “For a hematologist, the Hutch is the Holy Grail.”)
As is typical for a stem cell transplant, Brown underwent “conditioning,” an intense chemotherapy and radiation regimen that destroys the immune system to make room for transplanted immune cells to grow. On the day of the transplant – in a ward of the Berlin hospital named after a patient treated at Fred Hutch – he stopped taking his antiretroviral medication.
“The key reason I believed it would work is because [Hütter] was so certain it would work,” Brown said.
Hütter did not sugar-coat the rigors of the transplant itself. Nor did he outright promise an HIV cure, as hopeful as his plan seemed.
“It made sense that it would work,” he said. But there were risks, beyond the transplant itself. For one thing, sensitive tests done before the transplant had found that in addition to the strain of HIV that uses the CCR5 receptor to enter cells, Brown harbored traces of a rarer strain that uses a different receptor. Even if the transplant prevented infection by the more common strain, it was possible that the other strain would emerge to re-infect him.
“That would be a bad situation,” Hütter said. “But you can treat it [with antiretrovirals].”
In addition, medicine, Hütter pointed out, “is not always 100 percent. There will be patients for whom these procedures don’t work.”
In fact, in the years since Brown’s treatment, efforts to replicate his cure have failed to show the same results, mostly because the patients died from the cancer or the transplant before it could be determined whether their HIV was gone. In one case, the rarer strain emerged. That has not happened with Brown.
Although ever the scientist, Hütter acknowledges the role that chance – or luck if you have it – played in Brown’s cure. “He was at the right place at the right time,” Hütter said, undergoing treatment with an oncologist who remembered the 10-year-old HIV paper in a city with a good stem cell registry and access to a population with the needed mutation.
But he also points out the role that Brown played in his own treatment.
“What I admire about Timothy is his motivation,” he said. “You can’t cure cancer just with motivation. But when he came to us, he organized his life. The food was bad in the hospital, so he brought in his own food. He did workouts. Some patients lie in the bed and say, ‘Doctor, come cure me.’ He understood that he had to do his part. That’s unusual. We had a good doctor-patient relationship.”
The motivation was needed especially when Brown’s leukemia – though not his HIV – returned a year later, and he needed a second transplant. Recovery from that one was much more difficult, leaving him needing to learn to walk and talk all over again.
While Hütter and Brown are very different on the outside – one a married, mild-mannered scientist-physician, the other a gay activist who once modeled himself after Boy George – they share a straightforward manner of speaking, a dry sense of humor and a professed lack of emotionalism that can belie their continued close relationship.
“We don’t exchange Christmas cards,” cracked Brown.
“I miss always his birthday,” said Hütter.
The two men also share a passion in doing what they can to push for a cure for HIV that is easier, less risky and less expensive than what Brown endured and which everyone agrees is appropriate only for someone who needs a transplant primarily to cure cancer.
As an oncologist, Hütter was so unknown in the HIV field and a cure was considered so unlikely that it took almost a year after he first reported the results of Brown’s transplant for a medical journal to publish his paper.
What Hütter revealed Thursday night was the immediate – and overwhelming – reaction to the case by people with HIV.
“After the case become public, I received nearly every day emails, requests from people with HIV. ‘Please doctor, do the same for me, I give you any money.’” Hütter said. “I tried to answer every one. Sometimes it was my main work in a day to answer these questions.”
Today, others are working hard on finding answers for patients desperate for a cure. Some, including the Hutch-based defeatHIV consortium, are using Brown’s case as a blueprint for cure work centering on gene modification.
Led by virologist Dr. Keith Jerome and stem cell and gene therapy specialist Dr. Hans-Peter Kiem, the plan is to take an HIV-infected person’s own stem cells and knock out or disable the gene that acts as the HIV doorway, mimicking the genetics of someone who has natural resistance. The modified cells would then be returned to the patient.
Two other federally funded consortiums are investigating different approaches, and Hütter believes a cure will likely involve a mix, including a way to wipe out a reservoir of HIV that lies dormant in the body, hiding from antiretroviral therapy but roaring back if therapy is discontinued.
The overwhelming need for a cure was evident from the number of people who lined up Thursday evening to ask questions of Hütter and Brown. Perhaps the most poignant came from Moses Nsubuga, a member of the International Network for Strategic Initiatives in Global HIV Trials, who was visiting Seattle from Uganda.
“You are a symbol of hope in this struggle,” he said to Hütter and Brown. “I come from a continent where you have 70 percent of the people living with HIV. People are hopeless. These days, they hear so much about Timothy Brown. When I go back to Africa, one of them will ask me, ‘Is there a possibility of bringing Timothy to Africa so that he can interact with millions of people living with HIV?’”
“I definitely want to do that,” Brown said. “I want to help.”
Mary Engel is a former staff writer at Fred Hutchinson Cancer Center. Previously, she covered medicine and health policy for the Los Angeles Times, where she was part of a team that won a Pulitzer Prize for Public Service. She was also a fellow at the Knight Science Journalism Program at MIT. Follow her on Twitter @Engel140.