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News and Views

Thoughts on the Berlin Patient and a Cure for HIV/AIDS

An Interview With Martin Delaney

November 20, 2008

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Nearly everyone in the HIV community has been talking about last week's big news: A man in Germany whose HIV viral load has remained undetectable for two years following a bone marrow transplant even though he hasn't taken a single HIV med since the procedure. What do you think about this remarkable story?

First of all, it's really not new. I'm not sure why it's come up at this time. It was really reported back in February after the CROI conference [Conference on Retrovirals and Opportunistic Infections; to view poster, click here]. The only thing that's different now is that we've gone another several months beyond that.

Martin Delaney

Martin Delaney, Founder, Project Inform
Photo: Drew Altizer

I think it's a very interesting case, but I think it's premature to call it a cure. You really can't say that the virus is eliminated in the individual, because when you search for the virus in people where it's really been suppressed deeply, your ability to find the virus depends entirely on how much blood you're willing to take from that patient to find that one cell or another that happens to be infected. You just can't take the amounts of blood that are necessary to really find whether the virus has been eliminated.

But, that being said, what this does seem to suggest at the very least is that it has been suppressed to some level so low that it hasn't rekindled the infection of fulminant expression of virus. There aren't measurable amounts of new virus being made. So even if there is some HIV latently present or hidden away in cells, it is so suppressed that the body seems to be able to keep it from replicating again at any significant level. I think that's a really important learning point. It suggests that there will be ways to control HIV without the use of the drugs.

Obviously, the method that they used couldn't be applied widely. It's too expensive and too dangerous. But it could be done with gene therapy and perhaps even other methods. I think there is a lot of hope in this, but I think it's really important that we be careful not to oversell it.

Since this was discussed at CROI a little bit and I knew that amfAR [The Foundation for AIDS Research] met with the doctor and looked at some of the tests back in February. Haven't they found something out since then?

I think the amfAR meeting was much later than that. I think it was in September. It wasn't right after the CROI conference.

"The longer it goes without the virus starting to replicate again, the more impressive it becomes."

The only thing they can do, really, is to use more sensitive tests. We have tests using the standard amounts of blood that can read down between zero and 20 copies. But even if you reach zero on that test, you're only saying zero in that small amount of blood. To really say it's not there, you'd almost have to look at all of the blood in the human body. Obviously, that can't be done.

I think the main thing that's new is the length of time. At CROI they reported, I think, about 320 days post the transplant, and there was no sign of the virus. Now they're up to 600 days. That makes it more impressive. The longer it goes without the virus starting to replicate again, the more impressive it becomes.

I have one more question about the testing: Couldn't one test in his lymph nodes or the seminal fluid? Aren't there other places where HIV hides normally?

Sure. There are place that are what they call reservoirs and there are the lymph nodes. But, ultimately, it's going to come down to the amount of blood or the amount of tissue that you look at to really find whether you're down to the last few copies or whether it's actually gone.

People are calling this another KP-1461, which was another drug that held a lot of hope. Is this similar to that, or is this more hopeful?

I'm not even familiar with KP1461! [laughs] I've never heard of it before! I think this is more hopeful because this is an effort to cure the disease. It really moves us in that direction. I haven't seen any drugs that do that. Every drug I've seen is simply about suppressing viral replication and keeping it down at a low level.

Basically, what they've done with this person is build a new immune system using cells that are naturally resistant to infection from HIV. That's a radically different idea than just putting in more antivirals.

Could you explain on a patient level what a Delta-32 mutation is?

There's a certain mutation that a small percentage of people have which renders them incapable of producing what's called the CCR5 receptor. HIV needs that receptor in most cases to connect to and infect the body. What they've done here is they've used cells from a donor who had that mutation and therefore these cells don't have that CCR5 receptor and don't produce it. HIV will have a heck of a hard time infecting those cells.

If you get a bone marrow transplant, does that mean that all the cells will be replaced in your entire body with this new mutated cell?

First of all, this isn't just any old bone marrow transplant. We've had plenty of HIV-positive people who've gotten bone marrow transplants for a variety of reasons. In none of those cases did anything like this happen. What's different here was choosing this very special donor who had the mutation that we just talked about that prevents the cells from making the receptor that HIV needs.

Your question is a good one, because have they really -- through the bone marrow transplant -- have they eliminated all the other original cells, the ones that were susceptible to HIV?

The answer to that is probably no. But it may be that, over time, the new cells will come to dominate if not become the entire immune system, simply because they're the cells that are going to live while the HIV ones -- the infectable ones -- are going to die.

The other thing that was impressive about this is that this is all occurring in a man who's very ill. He has leukemia, so I don't know what the cure rate of that is, but he has immune problems beside HIV.

"I think people will have to look at this as something of a proof of concept. That's what you heard from David Baltimore and Tony Fauci and Bob Gallo. ... That this may not be a practical solution, but it suggests that other methods that might produce the same result are worth trying. In particular, that means the gene therapy approaches."

Right. That's correct. I don't really know what his condition is today. Obviously, they tried the bone marrow transplant, which is usually done as a last ditch effort. But apparently it worked if he's still alive at this point. But whether he's fully healthy or has a strong or a weak immune system, that's the kind of information we just don't have.

What do you think the next step should be?

I think all you can do is continue to follow the patient. I think it would also be important to get as much information as possible about his condition prior to the bone marrow transplant. We really don't know what levels of virus he had back then, what drugs he was on. Maybe somebody knows, but that information has not been made public. But I think it's critical to have that information to understand what really has taken place here.

Then, beyond that, I think people will have to look at this as something of a proof of concept. That's what you heard from David Baltimore and Tony Fauci and Bob Gallo. All three of them said the same thing: That this may not be a practical solution, but it suggests that other methods that might produce the same result are worth trying. In particular, that means the gene therapy approaches.

Do you know of any studies like that that are going on currently?

Yes, in fact. There's one fairly large such trial that's been going on for almost three years now and will report its data sometime in this coming year. It's not exactly the same type of genetic change -- it's a different model. But it's a similarly intent.

Then beyond that, there's at least a couple of other approaches that are planning to go ahead with pretty much the same thing here, where they will genetically alter cells taken from the patient, give them this mutated gene that prevents production of the receptor and then those cells will be grown in quantity and given back to the patient.

If somebody wanted to volunteer for either of these studies, how would they be able to do that? Would you know how they could?

I can't say that there's a startup date necessarily for them, but some of the groups that are involved in these include David Baltimore's group, also the City of Hope out of Los Angeles is working on this. Those would probably be the first two places I would look.

You've been one of the few people to really stay on the subject of cure.

Is there a think tank for the cure? You just mentioned two names: David Baltimore and City of Hope. For somebody who says, "I want to help move this forward, in whatever way possible," is there a Web site or a phone number or they could join?

There isn't a particular Web site, but there's a group of community organizations that have come together that includes Project Inform, TAG [Treatment Action Group], amfAR [The Foundation for AIDS Research], and FAIR, which is the Foundation for AIDS and Immune Research, all of which are now very committed to this search for an outright cure. I think we've all come to the conclusion that we're never going to treat our way out of this epidemic. Given the failure of vaccines to this point, it really behooves us to put more energy into looking or an outright cure. Any of those organizations would appreciate support and can share information.

There is a fairly large international group of researchers that are coming together around this as well. A couple of the drug companies in particular are involved in this. Tibotec and Merck are working in this area as is the National Institutes of Health.

It's an idea whose time has come and has caught fire. Despite the controversy around this particular example, I think it lends credibility to the field and I think even more researchers will show some interest in this in the coming years.

If you had a crystal ball and could predict the future in terms of a cure, are we talking about a cure in the next 20, 30, 40, 50 years?

The issue is: How long does it take to prove it? You might well see the first cures happen, I would think, within the next five to 10 years. The challenge, then, is that those just lead you to the necessity of then conducting large-scale trials to prove that this wasn't a fluke and that it can be done in a repeatable fashion.

That second part, the proof part, is going to take, easily, another five to 10 years beyond that, if not more. But there will probably be opportunities for people. I think, initially, the people that will be most likely to benefit from this will be people who have gotten into therapy very early in the course of disease. There are people who got into treatment programs during what they call the acute phase of infection.

Why them particularly?

Because the earlier you start treatment, the less loss you have of key memory cells and other important cells in the immune system. That's becoming more and more clear in recent years. It wasn't practical to put people on treatment really early in previous years because of the toxicity of the drugs. But we're dealing with a new generation of drugs now that are nowhere near as toxic as before. So it becomes practical for people to start treatment at a very early stage. When they do, it's probably possible to preserve more of the immune system and therefore make the idea of a cure easier.



  
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This article was provided by TheBody.com.
 
See Also
The First Man to Be Cured of AIDS: An Update on the Amazing Story -- This Month in HIV
Timothy Brown: The Other Side of the Cure
Tentative HIV "Cure" Presents a Guarded Sense of Hope
I'm Not Cured Yet
Is It Time to Celebrate the "Cure"?
Eliminating HIV/AIDS: How We'll Get to Zero
Can HIV Infection Be Cured?

Reader Comments:

Comment by: Peanut (Richmond, Va.) Fri., Dec. 2, 2011 at 6:19 pm EST
In 1981 I became hiv+, but didn't know it. I never showed symptoms of having the desease. Surprisingly I was diagnosed with full blown AIDS in March 1990. I had developed Auto Immune Hemolitic Anemia with a CD4 count of 198. The doctor told me I had about 2 years to live.
My count dropped to 167 before I started taking AZT as a treatment for this desease. I followed my doctors orders, and only missed a couple doses of my treatments since starting them. Over the past 20 years, I've lived with knowing I had this desease. My care givers now say I don't have AIDS, but I'm still HIV+. Does this mean I'm cured of AIDS. If I stay on the new medicenes I now take, will I get AIDS again? What determines a cure for someone that has been diagnosed for more than 20 years with full blown AIDS? My hardest part of living with AIDS, has been watching family, and friends that were very healthy die for other reasons. This is my life's story.
Reply to this comment


Comment by: Worried Mother (Austin, TX) Sat., Jul. 2, 2011 at 3:27 pm EDT
Is this "cured" man going to go right out and catch AIDS again? Is he now immune? Has he learned anything about being careful regarding infectious partners and circumstances?
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Comment by: Jads (SinG) Sat., Dec. 18, 2010 at 11:14 pm EST
I believe cure is possible for anything,but isn't this the result of man's lust?
So i strongly thinks that scientist shouldn't dwell into such issue. Had it not been their own cause, they wouldn't get such disease at the first place.
This isn't any propagation, we had to believe that anyone who had this disease is because they couldn't control themselves and defect to lust.
Come to think that its not the medicine but its human problem, if there is a cure the pedophiles and serial rapist will be the most happiest man on earth.
Reply to this comment
Replies to this comment:
Comment by: Mason (Fuquay, NC) Thu., Dec. 30, 2010 at 8:01 pm EST
How is it "man's lust"? You seem to not realize that many go undiagnosed and you can get it when you are born if your mother has it. And yeah, some pedophiles will be happy, but there are millions of decent people who need a cure too.


Comment by: Lady G (Baltimore, MD) Wed., Dec. 15, 2010 at 1:33 pm EST
I think this is a remarkable breakthrough for anyone who suffers from hiv or who has known someone that has suffered from the disease. I think it is important to find a cure instead of trying to treat it. Hiv/Aids is an epidemic all over and people seem to be contracting it at younger agers than before.

This is huge!
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Replies to this comment:
Comment by: Lawrence (Athens, OH) Tue., Dec. 21, 2010 at 12:08 pm EST
I agree that a cure is vital, as it is a inclusive of everyone. This is in contrast to a vaccine, which will forsake the tens of millions who are already infected. Add to that the fact that a cure honestly seems more promising than a vaccine, and I think we have a winner. What worries me is that current estimations for a "cure" consistently claim that they'll provide help to the small minority who began treatment within weeks of infection, with a cure-rollout timeframe decades in the future. Before we celebrate, we need to realize that this vision already leaves millions to die and dooms virtually everyone who is already infected.


Comment by: Mikey (San Diego) Tue., Dec. 14, 2010 at 5:23 pm EST
Evidently this cure is due to stem-cell research and treatment. This brings to mind one more reason to dislike George W. Bush since he banned stem-cell research during his Presidency.
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Replies to this comment:
Comment by: C. Vegas (Las Vegas) Mon., May. 16, 2011 at 5:51 pm EDT
To be fair, he didn't ban stem-cell research. He used federal funding to support existing stem cell lines (rather than creating new lines by destroying fetuses) and adult stem cells. The breakthroughs in research are coming primary from adult stem cells.



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