A Unique HIV Case Inspires New Research

http://www.kqed.org/.stream/anon/radio/quest/2012/07/2012-07-23-quest.mp3

For the first time in more than 20 years, the International AIDS Conference is being held in the U.S. In 2010, President Obama lifted a more than two decade old travel ban on HIV positive  people entering the country.  The conference begins July 23^rd in Washington D.C.  One of the topics sure to be high on the agenda is:  Where are we with a cure? More than 34 million people are living with HIV/AIDS worldwide, but only one person has apparently been cured of the virus.

Amy Standen spoke with the man known in some research circles as “the Berlin Patient.”

THE BERLIN PATIENT

Timothy Ray Brown was diagnosed with HIV in 1995, when he was living in Berlin. Nine years later, still in Germany, he received another devastating diagnosis: leukemia.

His doctor there had a novel idea. Maybe he could treat both diseases at once, by giving Brown a bone marrow transplant from a very specific type of donor, one who was CCR5 negative.

“It took 67 tries to find the right person,” says Brown.

The CCR5 mutation turns up in about one percent of Northern European descendants. It makes them naturally resistant to HIV infection.

Brown received two bone marrow transplants, one in 2007 and one in 2008, both from the same donor. The procedures were arduous, with lasting complications. But they also left Brown with a new immune system.

Brown, who is 46 and now lives in San Francisco, has apparently been free of the virus for about five years, and takes no HIV medications. Meanwhile, he’s watched friends die of the disease he no longer has.

“Being the only one in the world... I kind of have a slight guilt feeling about it,” he says.

Brown says he knows his treatment was risky and expensive, and that many researchers believe it's not a practical response to the worldwide AIDS epidemic. But he’s counting on science to change that.

Says Brown, “I’m hoping that when, and if, there is a cure it can be administered to the entire world. And I think that’s going to happen. I’m hoping for it."

THE TOOLS OF GENETIC ENGINEERING

California researchers are trying to replicate Timothy Brown’s treatment through a controversial gene therapy technique using stem cells. Andrea Kissack spoke with one of those scientists, Paula Cannon, a microbiologist at the University of Southern California.

You have been working with a technique that has proved successful in mice and will soon be expanding into human trials. How are you trying to replicate the apparent cure that has happened for Timothy Brown?

What we don’t want to have to do is do the same procedure that Timothy underwent. So let’s instead, how about the idea of taking some bone marrow stem cells from an AIDS patient, and engineering them so that we can make some of them also HIV resistant?

And the idea is we can do that, because now we have the genetic tools that allow us to go in and find the CCR5 gene in those stem cells and basically, like using a pair of scissors, we can cut it out. And then asking whether those cells that are now HIV resistant are gonna be powerful enough to actually sort of stop HIV in its tracks in patients.

So you are taking stem cells from patients and cutting out one protein and then putting the cells back, through a method like an IV?

Yes, we're trying to do the poor man’s version of what happened to Timothy Ray Brown. We’re going to use the tools of genetic engineering to snip out the CCR5 gene in a patient’s own cells, and in that way make some part of their immune system be resistant to HIV.

Last month there were some reports that Timothy Brown may not be virus free. What do you think about that? Is there a disagreement over detection levels or are there different kinds of cures?

By my definition of a cure which is for five years now he has had no replicating virus in his body, he is not able to infect anybody and he doesn’t have to take drugs. He is cured as far as I am concerned. If you want to get into semantics, one of the things that scientists are curious about is did we manage to remove every last trace of virus from his body or does he have some bits of dead virus floating around? I guess if you look long enough and hard enough – absolutely, we would find some traces of HIV. Importantly, if we are trying to develop ways to take lessons that happened to Timothy, and develop a treatment that can be given to people without needing a bone marrow transplant, to my mind the best possible outcome is that we find that Timothy still has these little remnants of HIV but despite that he is able to control it and he has cured himself through having this HIV resistant immune system.

You are using funds from the California Stem Cell Bond to help with this research?

That’s correct, and that’s been really, really important. When we first started this sort of work, we were doing it in collaboration with a biotech company in the Bay Area. And we were able to go to the California Institute of Regenerative Medicine, which is the agency that was set up after the stem cell initiative in 2004.

We were able to persuade them, I think, not just that in this way we could be using stem cells to really deliver a therapy to HIV-positive people, but also that the sort of techniques that we were developing in this way are going to have applications beyond HIV.

One of the challenges with stem cell therapy is the high cost of research and the distant payoff for the whole thing. So you are going to start the human trials in 2014 – what are you looking at in terms of seeing some signs if some of this gene therapy is working?

We have a series of benchmarks that we would look for. First of all, do we see any evidence that the CCR-5 negative cells are appearing in the patients after we give them the stem cells back? Are the levels of these cells increasing, which would suggest they have a selective advantage in the body?

We hope, of course, to end up with the situation, as happened with Timothy, whereby we can take the patients off the drugs, and they are themselves able to suppress and control the virus. I think for me, I’m very optimistic about it, because what we’re talking about are new types of medicine – gene therapies, cellular therapies – and we certainly don’t have the processes in place to make this cheap and easy yet. But I happen to believe that that’s just an engineering problem.

If this works, if these sort of therapies can really allow people to live without taking drugs and to cure themselves of HIV, there’s gonna be such excitement about this, such a big effort into figuring out how to do it at scale, to do it cheaply. We’re just gonna invent whole different ways of doing medicine.