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HIV Frontlines: The Doctor Who Cured HIV

An Interview With Gero Hütter, M.D.

June 19, 2012

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When you first thought to do this, this was a shot in the dark, right? Timothy's prognosis was pretty grim. No one had actually attempted this type of treatment before. Did you think, "Might as well give it a shot"?

Yeah. I would have felt better if I had tested it before. [Laughs] I knew it was probably possible. It's not easy to test the same condition in animals, but you could see some effects in animals.

In this case, it was clearly a shot in the dark. I studied the literature. I looked in PubMed, up and down, to see if there was anything published on this point: What happens if a patient who is HIV infected changes the CCR5 phenotype? And I found absolutely nothing. It's never been tested before, not even in vitro.

This was very surprising. It could be that no one really thought about this possibility. And the other explanation could be that they have tested it, it's gone wrong and no one got published. I was a little bit nervous about this point.

We were a little bit scared that we didn't really know what could happen: You have high selective pressure against the virus, when we changed this immune system to CCR5 depleted cells, and no one really could say how the virus would behave.

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[But then we realized that] the worst thing would be that he changes his tropism to the CXCR4 receptor, and then as long as he takes his antiretroviral medication, there's no harm for the patient. So we got optimistic that we could dare this experiment and that the risks are not too, too big.

I think it's easy for a lot of us to grasp on to this and say, "Here is the cure. Here is the future. Here is where it's going to happen." I'm guessing you've heard this kind of question a lot: "Is this the path forward?"

Yeah. If you look at the HIV research, we have no better answers for cure questions than what we have now with the CCR5 receptor, gene therapy. We have approaches in targeting, unmasking and killing, specifically, reservoir cells. But they are all connected with the cure question.

And the cure question, 10 or 5 years ago, was no real question. If someone said to you, "I want to cure HIV," all you'd have to say is, "You're mad. This is not possible. This is a retrovirus which degrades, and you can't get rid of the genomic material." This was the dogma of this case.

The way of thinking about cure has changed a little bit. This makes the process open for alternatives to the current antiretroviral therapy -- it does not have to be only the stem cell approach. There are other approaches derived from this case, which are also promising.

We've known for a while that the CCR5 receptor is the primary way through which HIV enters a CD4 cell. But there's still so much that we don't really know about the CCR5 receptor. How much have we learned over the past few years?

Very little. We know that the CCR5 deletion is much older than HIV, and the mutation appeared thousands of years ago. The distribution, what we see now -- in Europeans, this deletion is high; in Africans and Asians it is absent -- this is a distribution which happened in the last 10,000 years. There must be some kind of advantage for these carriers, and we don't know all the reasons why.

We don't know exactly the function of CCR5. We know that it probably plays a role in another infection, the West Nile virus infection. But all of the details are very unclear. There are some studies focusing on carriers of the CCR5 deletion, and whether they have high risk of any other disease. But these associations are very weak; there's no clear association of any disease with the deletion.

Why hasn't there been a Patient No. 2 yet?

We have had requests from other institutions -- taken together, I think we have now 15 other patients with HIV in need of urgent transplantation, because of leukemia, lymphoma, and so on. And some of them had just one [potential donor match]. Who gets that donor that was tested and was CCR5 negative?

Some had many potential donors -- 60, 120, such as Timothy had -- but sometimes mathematics fail. And the probabilities [of success] are 1 percent.

So this is a problem. I think it's a question of time. If you wait long enough, you will find a patient who will have the same conditions like Timothy.

The other point is that we don't have access to every patient who has the possibility to do this. There are many more patients with HIV who get transplants by allogeneic transplantation than we get information about. Because some institutions didn't really know about [the Timothy Brown] case. Some knew about this case and said, "Oh, this is so uncommon, this mutation; it doesn't make sense to test for it." They didn't start with it. If you don't start with the investigation, you will never find a second patient.

This is the biggest problem, I think: We have information about less than 5 percent of all these patients who get transplantation. If we have access to all of these and test them, the probability is much more higher to find a second patient.

Is this a uniquely European thing that you did? Could what you did with Timothy Brown not have been done anywhere else?

No: They tried it, too, in the U.S. But the circumstances are not like in Europe, or especially not Germany. We have in Germany a unique situation: We have 80 million Germans, and 3.5 million of them are registered in donor registries. It's very high. It's the highest proportion in the whole world.

Do you know how that compares to the U.S.?

You have 7 to 8 million in the U.S. But the difference, the second difference, is: These 8 million in the U.S. are derived from hundreds of stem cell registries. Every county, every state, every hospital, every institution has its own registry. And in Germany we have a central registry for all of these. So it's much easier to assess these registered donors.

That's also the reason why it works so well. You can do this in any country, but it works so well [in Germany] because we have this central registry, with a large number of registered donors. This was part of the success.

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