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|Jeffrey Laurence, M.D., Professor of Medicine, Director, Laboratory for AIDS Virus Research, Weill Medical College, of Cornell University|
Up until now, we've never been able to say that a person infected with HIV/AIDS has been cured. As I said, up until now.
You see, in 2006, something incredible happened in a hospital in Berlin. It was there, thanks to a unique and risky stem cell transplant, that a man may have become the very first person ever to be fully cured of HIV/AIDS.
This man's name has not been released; he's only known as the Berlin patient. But we know he's an HIV-positive American in his 40s who has been working in Berlin. In 2006, he was diagnosed with acute leukemia. In an attempt to treat his leukemia AND his HIV, the man's doctor -- Dr. Gero Hütter -- arranged for him to receive a stem cell transplant from a very special donor.
Ever since that transplant, the Berlin patient has had an undetectable viral load even though he hasn't been on HIV/AIDS treatment since before the transplant. The man has generously allowed scientists to take almost every possible biopsy and test, including the most ultrasensitive HIV tests available, but HIV has not been detected anywhere in his body. It's now almost three years since this operation and HIV still seems not to have reemerged. His story inspires new hope that some sort of gene therapy may be the key to an HIV cure.
Dr. Jeffrey Laurence, the chief scientist at amfAR, The Foundation for AIDS Research, has become the main contact in the U.S. regarding the Berlin patient, and he remains in close contact with Dr. Hütter, the Berlin patient's doctor. In September of 2008, Dr. Laurence organized a fascinating think tank of top HIV scientists to discuss the patient's case. They all agreed that the patient is "functionally cured." In this interview, Dr. Laurence tells us a little about that meeting, and about the Berlin patient's amazing story.
Welcome, Dr. Laurence.
Let's start from the very beginning. Tell us about the patient who appears to have been cured of his HIV.
I've been following this individual, trying to replicate what happened to him in others, for a couple of years now in the interests of research.1
This is a 42-year-old gentleman who's actually from Seattle, from the United States, but who is living in Germany.
He had HIV since about the age of 30, was successfully treated with a cocktail of drugs, and was doing very well with no detectable virus in his blood. His T-cell counts were over 400. He was basically a poster person for the way we can successfully treat HIV disease now. He was doing fine, with no complications.
Then unfortunately, in March of 2007, at the age of 40, he developed a kind of leukemia -- we call it acute myelogenous leukemia, or AML -- that typically requires a bone marrow transplant. He went to a hematologist, Dr. Gero Hütter, in Berlin and was treated with the standard drugs for this type of leukemia. Seven months later, this patient experienced a relapse of his leukemia. (And that's not uncommon; that happens maybe 50 percent of the time.) This time, he was again given the standard treatment for patients with leukemia who are in relapse. But he was also given what we call a stem cell transplant. It's like a bone marrow transplant, except instead of extracting cells quite painfully, and under anesthesia, from a donor's bone marrow, we just take it from his or her blood.
What was unusual about the particular transplant done on this patient was the extra step taken when selecting the donor. Normally, when locating a potential donor for a person with or without HIV and leukemia, we would go through the worldwide registry of people who had agreed to donate stem cells or bone marrow.
There are about 13 million people who are on this computerized donor list now. The Berlin patient's physician went through the 13 million people and found 232 people who were identical tissue-type matches for this patient. Any one of those 232, if they agreed to come in and donate their stem cells, presumably would have been an excellent match for this patient. But with the patient's approval, the doctor went a step further.
The doctor had a great idea. He said, "Why don't we try to do something a little better than that? Why don't we think about curing not only your leukemia with the stem cell transplant, but also your HIV?" The thought there was, let's take all 232 potential donors and screen them for a genetic mutation that would make those cells resistant to getting infected with virtually all known types of HIV.
This is a relatively infrequent -- I wouldn't say rare -- condition, since it's found in somewhere between 1 and 2 percent of white Americans and Western Europeans; in about 4 percent of people from Scandinavian countries; and in no Africans, African Americans or Asians, which tells you something about the genetics of racial splits way back when.2
What is this genetic mutation due to?
The mutation is called delta32 CCR5, and it was discovered about 10 years ago.3 In fact, one of the groups that discovered it did so with funding from amfAR (The Foundation for AIDS Research), an organization that I work with.
It's known that if you're lucky enough to have this mutation, the delta32 CCR5, from both your parents -- something we call homozygous, technically -- you are resistant to getting infected by most forms of HIV.
The transplant was done, and it was successful. About a year later, the patient had a relapse of his leukemia and required a second transplant. Now, in this time, the patient had no HIV viral load and had good T-cell levels despite the fact that his antiviral drugs were stopped.1 His virus didn't come back and his T-cell levels remained high -- that's the miracle of this patient.
Could you explain what the purpose of a stem cell transplant is and exactly what happens during the procedure?
What we're trying to do is kill off all of the leukemic cells in a person's body. Leukemia comes from cancerous white blood cells, and the process of killing off those cells means treating the person with as many drugs that are toxic to blood-forming cells as the person will tolerate.
In this instance, the person was 40 years old and could tolerate things very well. He was given radiation therapy to his whole body. He was given two immunosuppressive drugs. He was given a serum prepared in a rabbit immunized with human T cells -- like kind of an antibody to kill off a person's T cells. He was also given a multitude of drugs that cannot only kill leukemia cells, but can also kill immune cells.
So he was basically an empty vessel. All of his own stem cells and all of his own bone marrow blood-forming cells were utterly destroyed. If you just left him alone, he would die within a week or two. But this person obviously was rescued, as you need to be, with stem cells taken from the blood of the donor. (Stem cells can also be obtained from bone marrow.)
All of the blood-forming cells in this Berlin patient's body were replaced with donor cells. There was nothing that was genetically identifiable in terms of blood-forming cells -- in terms of T cells susceptible to HIV infection -- that looked like the recipient. It was all from the donor.
As I mentioned, this was a very special donor who had been selected. A Wall Street Journal article was written about this case.4 The article subheading was, in part, "Many Thanks, Sample 61," because of the 232 people that they could have used for this transplant, whose tissue types were perfectly reasonable to give to the Berlin patient -- and they tested every single one of them -- number 61 turned out to have the delta32 CCR5 mutation that would make the cells being put back into the body of the Berlin patient resistant to virtually any kind of HIV we know of.
To answer the question, "What if there's a virus lurking in this person's brain, hair follicle or fingernail?" Whatever you want to postulate? And what if that virus were to pop out from hiding, from a latent state, from dormancy? It would presumably be prevented from taking over this person's body again and growing as if he had been newly infected, because the cells that he was given from the donor are resistant to infection by HIV. That's the key part of what we've done here.
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