“I predict that, in a couple of years, his HIV antibody test will be negative.”
[Editor’s Note: Since we conducted and posted this interview in 2009, there have been many developments in the story of Timothy Ray Brown, formerly known only as the “Berlin patient.” In addition to this article, we encourage you to read “Tentative HIV ‘Cure’ Presents a Guarded Sense of Hope” for an update on Brown’s condition as of late 2010, as well as the perspectives of two of our HIV-positive bloggers — Ibrahim (who is encouraged by Brown’s story) and Thomas DeLorenzo (who remains more skeptical).]
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.
An HIV-Positive American Man in Berlin Needs a Stem Cell Transplant and His Doctor Tries a Daring Experiment
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.
Some people don’t understand how HIV enters a cell. Could you explain that and why CCR5 is important? Any virus, any bug that you get infected with only does you damage because that bug has gotten inside your cells. If it’s floating around not activating anything, not harming anything, it’s irrelevant and it’s going to get washed out.
HIV gets into critical cells of the immune system — the T cell, basically — through two doors. One door is called CD4, and that’s why we count CD4 cells. But the critical door is called CCR5. If you don’t have CCR5 sitting on top of your T cells, it is virtually impossible for you to be infected with virtually all strains of HIV.1So, by having this mutant given by this donor, the person’s cells are resistant to being infected with HIV. You could ask, “It’s a mutation that is found only in about 1.5 percent of Caucasians, 4 percent of Scandinavians. Why is it there? Where’d it come from? Is it harmful?”
We know it prevents HIV, but surely evolution didn’t create this mutation just to stop one from getting HIV 100,000 years ago (or whenever it’s perceived that Caucasians and Asians separated from Africans in the cradle in Africa).
Truthfully, we don’t know why. The hypothesis has always been that there must have been some huge epidemic way back when that was present in Western Europe, in Scandinavia, that didn’t occur in Asia and didn’t occur in Africa, that wiped out so many people who didn’t have this kind of spontaneous mutation.
Therefore, among the people that were left to breed, many, many more of them had this mutation. At this moment, we may never know what that catastrophe was tens of thousands of years ago that could have protected some people that had this mutation, and led to the death of so many others.
The Black Death [bubonic plague] obviously comes to mind, but people have tested the bacterium that we believe caused the Black Death in the 13th, 14th to 15th centuries and it’s unrelated to CCR5, so we may never know.
But anyway, CCR5 is the key door for HIV to get into a cell. And the delta32 CCR5 mutation means the door ain’t there. There’s no way for the virus to get in. Therefore, it just kind of knocks around helplessly and eventually dies off.
What Tests Confirmed No HIV Was Present in Berlin Man?
Dr. Laurence, what tests were done to confirm that there was no HIV left in the Berlin man’s body?
An article was published about this patient a few months ago in The New England Journal of Medicine.1 Just before the article was published, I organized a think tank sponsored by amfAR at MIT [Massachusetts Institute of Technology]’s Endicott House, where we got together scientists from around the world, including Dr. Hütter, to talk about what additional tests could be done apart from what had already been done in Germany.
For example, in The New England Journal of Medicine article, it mentions that before that transplant, the patient had an undetectable viral load. Of course, he was on drugs. When he was taken off the drugs, he still had an undetectable viral load, but the tests that they were using are the standard kinds of tests that a person with HIV might get when he or she walks into a doctor’s office (i.e., tests that can’t detect less than 50 copies of virus in 20 drops of blood).One of the scientists that I invited to this meeting said, “50 copies per 20 drops? I can get less than a third of a copy of virus in 20 drops.” So we had that scientist test the patient’s blood and it was negative. So there is no virus by the most sensitive ways that you could possibly look for virus.
Did you also give this man an antibody test?
That’s very important. His antibody test would be positive. If you vaccinate someone, say, against the measles or polio and test them for antibodies a year or five years later, he or she will be positive for antibodies. But as you start getting on in time from that initial vaccination — and it’s why we give boosters against certain diseases — the antibody levels fall off. And that’s what’s happening to this patient.
It has been about two and a half years since the patient has been off of all of his antiviral drugs and had the transplant, and he still has absolutely no detectable virus, either active virus or latent virus.
His antibody levels — we call them titers — are declining just the way you’d expect them to if you’d given someone a vaccination against HIV and then looked at the levels of antibodies. They’d be very strong in the beginning, but would weaken if they are not re-exposed to the virus.We believe this person has no HIV in his body and therefore there is nothing to re-expose him, so the concentration of HIV antibodies in his blood is decreasing. I predict that, in a couple of years, his HIV antibody test will be negative.
In response to the article that appeared in The New England Journal of Medicine, Dr. Jay Levy — who’s an outstanding AIDS scientist from the University of California in San Francisco [UCSF] — wrote an editorial titled “Not an HIV Cure, but Encouraging New Directions.”5 In his editorial, he said the reason he used the title “Not an HIV Cure” is that there’s a lot of evidence from a lot of other studies that HIV can be “lurking” around in cells. What he means is we still wonder: “Could it be in the brain? Could it be in the liver? Could it be in the intestine? Could it be in the stomach?”
This person, I think I mentioned, had a relapse of his leukemia and needed a second stem cell transplant in an attempt to re-cure his leukemia.1 They used cells from the same CCR5-negative donor. After that second transplant, the patient developed complications from the transplant.He seemed to go through the first transplant with flying colors, though he had a little bit of liver upset, which resolved. But he had many problems from the second transplant itself, which are not unexpected in people who get two transplants.
One of the problems was that he started developing some mental changes. People worried, “Is it related to the transplant? Could it be related to HIV lurking in his brain?”
So he actually had a brain biopsy, in addition to biopsies of his intestines, liver, lymph nodes, bone marrow — basically, every part of the body that can be biopsied. The best part in answering the Levy editorial was including his brain. All were negative for virus. There is no virus in this person’s body out to two and a half years off of all anti-HIV drugs.
This is certainly a functional cure, in the sense that there is no need for anti-HIV drugs and no decline in the patient’s immune system. But I would say that, at this point, with all the tests that have been done by scientists throughout the world that I’ve arranged to have samples sent to, that this patient is as close to a cure as anyone could possibly document — apart from if the individual were to die and have every single part of every single body organ tested. There is no virus in this person’s body. –TheBody