For the First Time in History Man Cured of HIV | Hacker News Reader

For the First Time in History Man Cured of HIV

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172 pointsazazo48 comments

From my friend, an HIV researcher:

Me: So is this genuine progress or breathless "science" journalism?

Him: A little of both to be honest. They basically replaced the man's entire bone stem cell population with a donor's to "cure" him. Which only works for one type of the virus. Which only works if you have an exact match for a bone marrow donor. Which only works if the exact match happens to have the super rare CCR5-32 mutation that makes them immune to that one type of virus. And you get to take immunosuppressants for the rest of your life because you have another dude's bone marrow in you. That being said, they cured HIV.

"This is not prime time to me at all. This is a very unusual situation that has little practical application for a simple reason. This donor not only had to be a good compatible match, but the donor had to have a genetic defect of cells that do not express the receptor that the HIV virus needs to enter the cell."

"This patient is trading one poison for another. He may not have to be on antiretroviral drugs anymore, but he has to take immunosuppressant drugs now to prevent the rejection of his transplant cells. Again, what this is, is an interesting proof of concept, but it's absolutely impractical."

- Dr. Anthony Fauci, director of the National Institutes of Allergy and Infectious Diseases

Source: http://www.foxnews.com/health/2010/12/14/doctors-claim-hiv-p...

This procedure has a >10% mortality. The annual mortality from HIV in 2010 is how many orders of magnitude lower than 10%?

And why were they willing to do this risky procedure for this patient? Hint: not because of his HIV.

This is an example of a huge story that nevertheless got enormously overblown.

Whether the treatment is is worse than the disease is less relevant here than the fact that this proves it is in fact possible to cure. With that knowledge, we can pursue techniques that won't hopefully won't have such drastic consequences.

Most researchers already agree that it will be soon possible to cure HIV. Antiviral therapies, while not yet well known, are becoming mainstream. I wouldn't call this a "cure", but rather evidence that one person's immunity to a specific form of HIV can be transferred to an person infected with that form to prevent it from replicating. It supports existing claims about the role of CCR5 in HIV's life cycle and the protective effects of its mutation. There is no reason to preface this with "For The First Time In The History Of Man" or anything so dramatic.

If you have friends who have HIV/AIDS, you'll be more appreciative of the dramatic flair.

Since this cures you for life, comparing it with the annual mortality rate doesn't seem appropriate. Better to compare the average life expectancy with and without the procedure.

Is taking the immunosuppressants for the rest of his life aspect unique to his particular bone marrow transplant procedure? My father had a bone marrow transplant several years ago, and was off medication within a year IIRC. (At the least, I know he takes no medication currently.)

The article does say 'stem cell replacement'. I'm not medically savvy enough to know how different that is from the 'traditional' bone marrow transplant. Can someone help me out?

Couldn't they put the original bone marrow in a box somewhere, wait until the borrowed marrow has done it's job and then replace the original one, to not have to take immunosuppressants?

I don't think bone marrow transplants are quite that cut & paste.

Someone should file a bug report, cos that is obviously a design flaw.

Cut and paste will be in the next release :-)

Of course, but with a bit of research it might be a better long term alternative; suppressing the immune system isn't something that'll ensure longevity.

Your chance of survival would go from (0.9) to (0.9*0.9).

Also, this paper hasn't actually proven a cure. It has clearly demonstrated long-term suppression. However, by replacing the CCR5-deficient T cells with his regular cells, you'd certainly test the hypothesis. There is also the risk that you would be reintroducing HIV-infected cells.

Isn't there the issue that his original bone marrow (which you've temporarily removed) is probably infected with HIV? Returning it at a later date would reinfect him.

However, what this does show is that CCR5 is more than simply protective (which we knew) it could, if properly targeted via therapeutic intervention, eventually cure someone.

This is very similar to a south park episode. Guy runs to a bunch of dying, dirt poor people in affrica "We have the cure for AIDS! You just have to inject 500,000 dollars directly into your veins! Woo!"

Basically this "cure" is of the type where the guy was about to die, he underwent a procedure that had a 50% or so survival rate, upon success he is cured of most strains of HIV.

Hey its great, we know this thing can be killed. Lets see if we can put that knowledge to work. But this is not a generic "cure".

From my understanding HIV is a virus that infects immune cells and uses them to replicate. What happened is that this man had his immune system almost completely destroyed to defeat leukemia, and received stem cells from a donor with the mutation CCR5 known for its reduced risk of HIV infection.

Basically they destroyed the HIV's food source, and likely (at least temporarily) changed the man's new immune cells to the CCR5 variant in them that reduced the effectiveness of the HIV's ability to replicate.

Again, from my lay understanding, HIV changes its cell protein markers to avoid being attacked by immune cells. Often there are multiple HIV variants with different protein markers at one time active in a person.

IMO all but the 'newest' variant likely died of attrition, leaving one or two HIV protein marker variants that the new highly bolstered CCR5 mutant immune cells managed to latch onto and defeat.

I could be way wrong, but from my understanding this is the closest 'model' I can think of for how this would work. However, it's past my usual end-of-day so it may just be gibberish of an overtired mind.

Nitpick: Viruses don't consume food for energy, they feed off of the energy metabolism of their host cell. CCR5 is a receptor that HIV binds to while entering human cells. If it is mutated in a certain rare way, HIV has a hard time entering cells, and it needs to be inside the cell to replicate. By swapping out this guy's immune system with one that has mutant CCR5, they've prevented HIV from replicating in his body.

HIV is also active with glial cells. AIDS dementia complex is a direct result of HIV infection of these kinds of cells (most likely). It would be really interesting to see if there is still virus in the patient's brain, and if so, what effect it will have on him going forward.

A sample of one is not a cure.

There is a controlled Clincal Trial in the recruiting stage for participants surrounding CCR5 and its ability to block HIV.

http://clinicaltrials.gov/ct2/show/NCT00842634?term=806383&#...

Sad not to see that citation in every single one of the attached articles pounding the drum.

Thanks for the link. However:

This case is a cure. HIV is pretty well known to not go away on its own (except under the circumstances described in your link). This treatment is almost certainly responsible for him no longer having HIV.

The notion that a cure must be widely applicable in order to really be a cure is rapidly becoming obsolete: many hypothesized or developing treatments involving stem cells or genetics or bacteriophages are very specific, often to the level of needing to be manufactured/cultured/etc. on a per-patient basis. This makes them less useful, but really has nothing to do with their ability to actually work.

This case is not announcement that a miracle drug will be hitting pharmacies in a few decades, but it is proof (or at least, very strong evidence) that HIV can be defeated in vivo.

1. The notion that a cure must be widely applicable is the foundation of clinical medicine, even with personalized medicine. You simply can't run clinical trials with a sample size of 1. Just because an individual treatment is tailored to the patient doesn't mean the process and plan of action is generated new each time. The OP is stating how there is no way to generate the 'curative' stem cells and the odds of them appearing in natural populations is extremely rare. This case is an awesome but exceptional situation, and is not a basis to claim a breakthrough in the fight AIDS. As a proof of principle, even anti-retrovirals show that an individual can be healthy post-infection.

2. There are no FDA approved therapeutics for disease that use bacteriophage, there is only some things as preservatives for meat. Most treatments of genetic disorders are generally nonspecific - they treat symptoms and gene therapy is still a developing field. Even in that case, the delivery vector is usually generalizable - usable in many patients with slight individual modification.

3. in vivo refers to in glass, or in an experimental set-up, this is most clearly not in vivo.

>even anti-retrovirals show that an individual can be healthy post-infection

Anti-retrovirals only do so much - they have to be taken for the patient's whole life. This is different, they are claiming that HIV has effectively been eradicated in a living body, which just hasn't happened before. This isn't meant to be a clinical trial, it's the only living proof we have that we can kill all the HIV without killing the patient.

And you're mistaken about in vivo. In vivo = "within the living", in vitro = "within glass" (& "in silico" = "within silicon", ie. simulated on a computer).

Do you consider organ transplants to not be "cures" of any disease? I've yet to hear of even a potential method for growing vital organs from scratch, and even the methods using donor cells seem to lack FDA approval.

If you do believe that organ transplants can cure a disease, then there must be some threshold of donor commonness that divides organ transplants and this treatment. Where might that line fall?

The sample size has to be large enough for the results to have statistical significance. If something happens in the patient that never happens in comparable cases, and you have piles of information about suitable controls, then you can place a high certainty in the treatment being able to work. You don't have a success rate, but nobody's claiming one.

I think this is the original article: http://www.nejm.org/doi/full/10.1056/NEJMoa0802905

I would like to see the a Medical Journal Article referenced here. Needs more testing, but certainly a great success, no matter what.

I have a friend of mine who moved away, so I now mostly keep in touch via his blog. I've known him since 1995, and he's been HIV positive since I've known him.

That said, within the past few years he was admitted to a similar clinical trial that has all but eradicated the presence of HIV in his system. For at least the past 6 months (it's under very close watch) there has been absolutely no detectable traces of HIV in his blood.

This is far outside my general sphere of knowledge, so I'm apt to speak unintelligently on the subject if I go into deeper detail, but it goes without saying that we're ecstatic for him, his family, and everybody else in the world plagued with the virus.

My biggest concern is the cost of the treatment. He's in trial, so it costs him effectively nothing, but as the treatment is perfected and rolled out to the masses, I have very little doubt that this will be affordable to only those with the very best insurance or those with very fat pockets.

I'll reserve judgement on the morality of that, as I do believe the presence of an expensive cure is infinitely better than the absence of a cure, but I'm just hopeful that they can manage a way to ensure that it does in fact work as they believe, and refine the process to such a degree that it becomes affordable.

This guy ended up with brain damage most likely from the treatment. If that's part of the cure then I'm not sure it's worth it.

    20th century: "HIV is a virus, and viral diseases cannot be cured." [1]
    21st century: "Counterexample!"

[1] My understanding of diseases is weak. I remember being told that bacterial diseases can be cured more or less trivially, but viral diseases can only be vaccinated against.

Viral diseases most definitely can be cured with current research techniques. If anything, they present a much easier target than cancer or other end-of-life diseases, because viruses are comparatively simple little infectious agents and comprise the sole cause of the disease, so a cure only needs to attack one thing. Their genome is on the order of a few thousand base pairs, usually only 10-100 genes. You should check out all the new antiviral drugs that have been developed over the last decade, it is really the product of the new age of genome-level research. [1] The main problem in developing antiviral drugs is toxicity, because viruses co-opt certain parts of the cell and have proteins that are usually similar to normal human genes, and you have to find treatments that only target the viral activity. For example, the first commercially successful antiviral [2] targets reverse transcriptase, which performs a function that normal human cells never do (transcribe RNA -> DNA).

[1] http://en.wikipedia.org/wiki/Antiviral_drug

[2] http://en.wikipedia.org/wiki/Acyclovir

Some viruses are better than others at staying around. Retroviruses, such as HIV, have an enzyme called integrase that adds the virus' genes into your DNA. That makes it particularly difficult to get rid of. Most viruses aren't that good.

So, it's entirely possible that the rogue code remains unactivated in his cells but remain rather ineffective because the white cells come from a different lineage due to the transplant.

Funnily enough Retroviruses are also the major vector in gene therapy.

Retroviruses incorporate into the host genome and is important for gene therapy. This allows for a long lasting effect and is essential depending on cell type. Different cell types have different turn-around rates. If the gene of interest is for a protein, you need incorporated DNA for continual expression.

Don't forget that you can use viruses to kill bacteria:

http://en.wikipedia.org/wiki/Phage_therapy

Yes, viruses are both terrifying and awesome :)

That isn't accurate.

The body frequently cures itself of viral diseases.

Do you mean can doctors cure a viral disease? That too isn't really accurate, since what they did is get the body to cure itself - which isn't that different (in principle) from a vaccination (although it's a massive difference in practice).

BTW, this isn't really the first time.

It's at least the third time.

There was a case where someone got a bone marrow transplant (because of cancer) and the donor was immune to HIV which cured the recipient.

Also some people are naturally immune.

There has only been one case; all the articles you remember reading (including this one) reference this one study.

But that was in the news 2 years ago - why are we talking about it again?

http://www.time.com/time/health/article/0,8599,1858843,00.ht... http://news.bbc.co.uk/2/hi/7726118.stm

This is real science. It took three years to be sure; and for an announcement like this, the investigators want to be sure before they put their reputations behind it.

I've never heard anything to the effect of some people being naturally immune to HIV. I've heard of people with much higher resistance than normal, but not immunity. Could you please provide a source? It seems to me that people who were naturally immune to HIV would provide a powerful tool to doctors researching potential cures, and thus would be major news.

It was and is major news, just google hiv immunity - tons of links come up.

For example: http://www.sciencedaily.com/releases/2010/05/100505133250.ht...

Also - that's exactly what this case is - the donor was naturally immune to HIV.

This is the same case.

I know someone with MS who went through something similar with encouraging results. I believe it was a mix of chemotherapy to suppress her own immune system followed by a bone marrow transplant from a healthy donor.

Nice to hear this kind of break through! But is it attached to some kind of controversy like stem-cell research/cloning? If new bone marrow is the cure, then the next step might be a cloned bone marrow so you don't need to have pills for ever! This might be opening a hole into advanced genetic research on cloning stuff!!!!

I hope this isn't similar to Assange getting bail and NASA discovering arsenic based life.

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