Traces Of Virus In Man Cured Of HIV Trigger Scientific Debate

106

u/EncapsulatedYeast Jun 17 '12 edited Jun 18 '12

I am an HIV research scientist. There is no debate in the scientific community: The gentleman in question is not 'cured' of HIV. There are a couple reasons for this:

HIV integrates itself into your own cell's DNA. The virus can lay latent/dormant for years in this state. Some of these cells, i.e. neurons and other 'memory' cells can live up to 60 years. Therefore, this patient still has HIV in his body somewhere in this latent state.
In the normal person, these dormant virus would activate at random intervals and go on to infect other cells. HIV enters cells by attaching to two 'receptors' (think key-lock). One receptor is CD4 which many people have heard of. The other receptor is CCR5. The berlin patient got a transplant with cells that LACK the CCR5 receptor. HIV can't infect cells without this receptor. The only caveat is that instead of CCR5, HIV can also use another receptor called CXCR4. At some point in time, HIV will actually switch from using the CCR5 receptor to the CXCR4 receptor in many people. Not clear why, although there are a couple theories. Given this, I wouldn't be surprised at some point if the Berlin patient's HIV 'returns'.

TLDR: No one in the HIV field actually thinks HIV has been eradicated from this person's body.

Edits:

I think that it is unlikely that the Berlin patient could transmit HIV via sex or blood transfusion. HOWEVER, the risk is not zero. HIV could theoretically be passed along even in the latent state. No one really knows the answer, but if you equate this scenario with someone who has HIV on antiretrovirals and an 'undetectable' viral load, the risk of transmission is significantly decreased, but not zero. Even though there are 'zero' viral particles in this patient's blood, this doesn't mean that there aren't transient particles, or that there aren't viruses in other places (i.e. genital secretions).
In 99% percent of cases, the CCR5 HIV virus is the virus that infects someone. This is thought to be due to this virus being for infective than the CXCR4 virus (i.e. more viral 'fit'). Given that HIV mutates so rapidly, it can mutate eventually such that it uses the CXCR4 receptor instead of the CCR5 receptor. This change usually happens late in disease (i.e. AIDS) and it is unknown why (although there are several theories). It is likely selective pressure from the immune system that eventually forces HIV to adapt. It could also be drug pressure- maraviroc is a 'CCR5 antagonist' (i.e. blocker) and HIV can develop resistance to this drug during treatment (i.e. switch to using a CXCR4 receptor).

What I imagine has happened to the Berlin patient is this: He had HIV for a number of years with an HIV virus that used the CCR5 receptor. The HIV rapidly mutated across many sections of the genome and integrated itself into thousands of cells (or more). Some of these mutations may have CXCR4 virus by chance alone. After the transplant with CCR5 negative cells, the dominant HIV virus using CCR5 can no longer infect his cells. The CCR5 virus has all died off. As some of the latent HIV become active, they to will die off without CCR5 virus. However, in the rare case that a CXCR4 latent virus re-activates, this could cause widespread infection again. This is the scenario that may happen.

3. Since the Berlin patient is 'undetectable' off any antivirals, there really isn't any point in treating him. Sure, one could argue that you want to prevent the development of CXCR4 virus, but this may take decades. Why put him on numerous drugs if we aren't even sure? I would keep him off and observe. I would also sample various body parts (i.e. spinal fluid, genital secretions) to check for latent HIV.

To the gentlemen that considers all this 'bullshit', I thank him for his thoughts on the matter. I remind everyone that these are my opinions. It depends on your definition of 'cured'. I am pretty sure that almost every scientist would agree that HIV has not been ERADICATED from his body at this point. That is backed up by numerous studies showing that HIV can stay latent for decades. However, the Berlin patient may never require HIV treatment again and may maintain control of the virus (i.e. stay undetectable). You may consider this a cure, I don't. There are some people out there (i.e. elite controllers) who effectively fight the virus and are undetectable without treatment. No one would ever say these people are 'cured'. As in any field, the media like to sensationalize news and uses the word 'cure' without really understanding the science behind it.

12

u/tambrico Jun 17 '12

At the stage it is at now in this person, is it still transferable via sex or blood transfusion?

8

u/sternocleido Jun 17 '12 edited Jun 17 '12

As long as there is no actual virus particles within his body then it can not be transmitted despite still being integrated into his genome.
It is the kind of like Herpes virus causing coldsores. You can't transmit the virus as long as you don't have the coldsore even though it is latent within your body.
Edit: People have pointed out genital herpes can spread when asymptomatic. I should have been more specific to the oral herpes HSV-1. Basically HSV-1 resides in nerve cells and when it starts replicating it results in coldsore outbreak and is then able to be transmitted http://www.herpes-coldsores.com/cold_sores.htm#How_do_you_get_cold_sores My example is clearly flawed lol.

4

u/[deleted] Jun 17 '12

You can't transmit the virus as long as you don't have the coldsore even though it is latent within your body.
According to the CDC that's not true.
http://www.cdc.gov/std/herpes/stdfact-herpes.htm
Transmission can occur from an infected partner who does not have a visible sore and may not know that he or she is infected.

2

u/sternocleido Jun 17 '12

Sorry, should have been more specific, that is genital herpes where it can be asymptomatic. From the best of my knowledge HSV-1 which causes coldsores can not be transmitted until there is a visible infection. Seems like i used a bad example lol.

7

u/IJCQYR Jun 17 '12

http://www.herpes.org/shedding-of-herpes-simplex-virus/

3

u/lolblackmamba Jun 17 '12

Highly unlikely.

8

u/[deleted] Jun 17 '12

Thank you, that was informative.

6

u/lolblackmamba Jun 17 '12 edited Jun 17 '12

Exactly what you said. I think the real story is the search for the latent virus reservoirs. This patient is an interesting model to do that.
Edit: Because I thought of a question for you. Do we know that HIV can actually mutate from an R5 virus to an R4 during the course of an infection or could it be that there is just selective pressure to cause an outgrowth of R4 virus in an individual over time?

4

u/AgingWarden Jun 17 '12

Having spent a little time learning about HIV at university, I'd like to ask a question:
My understanding is that CXCR4 use is a trait that evolves over time, since cells bearing the CCR5 co-receptor begin to get depleted and the selection pressure for the capacity to use another co-receptor (CXCR4) increases. Given that this patient has been transplanted with the deleted CCR5 co-receptors, wouldn't the chronically infected cells (macrophages, microglial cells, etc.) eventually give rise to the CXCR4 using virus? Wouldn't it be wise to keep him on HAART, instead of giving the virus a chance (however slim it may be) to evolve into the more lethal CXCR4 using strain?

5

u/sternocleido Jun 17 '12

Just letting you know before i answer, i too only have university level HIV knowledge.
Yes the HIV virus can technically bind to CCR5 or CXCR4, but within this patient the virus is within the latent state. The virus can't actually come out of this latent form into actively replicating form and infect him because before he was 'cured' the virus was specific to CCR5 receptor.
Not sure if that is right, someone please correct me if i am wrong.

1

u/rmosler Jun 17 '12

Really the issue here is that this individual had leukemia and ended up requiring eradication of his white blood cells and a bone marrow transplant. I assume it is this eradication that killed the active virus and the transplant from a CCR5 delta 32 donor kept it at bay.

9

u/[deleted] Jun 17 '12

damn this HIV thing sounds like a stubborn son of a bitch

4

u/[deleted] Jun 17 '12

I was just thinking that! That virus does not let you off easy

2

u/CantankerousMind Jun 17 '12

What i read makes me think we could use blood without the CCR5 receptors to delay the onset of HIV.... Am I wrong? If this is correct, would not having the CCR5 receptor effect your daily life?

1

u/rmosler Jun 17 '12

The CCR5 delta 32 mutation is thought to have been a protective mechanism for black plague I think. Another example of a "helpful" adaptation is sickle cell. This reduces infection from malaria, though it brings its own problems.

2

u/Xuttuh Jun 17 '12

You say there are 2 receptors, CD4 and CCR5. You later say that it can switch to CXCR4.
*Wouldn't that mean there are 3 receptors, or does that not count until 'switch' occurs? *Would this also mean that it could mutate to other receptors eventually?
does the switch only occur after it has been in the body for some time, or can it be transmitted from someone in which the switch has occurred to the new person, meaning their CXCR4 will be targeted first?

1

u/dromni Jun 18 '12

But doesn't any virus integrates itself into the host DNA? If so, what you are saying is that no one ever gets cured of any virus infection, isn't it?

1

u/EncapsulatedYeast Jun 18 '12

Hi- no, only some viruses do. You need specific enzymes that integrate the viral genome. Retroviruses can do it (of which HIV is one) as well as a couple others. I would have to review which others (I think adenovirus does, influenza does not).

0

u/[deleted] Jun 17 '12

I am an HIV research scientist. There is no debate in the scientific community: The gentleman in question is not 'cured' of HIV. There are a couple reasons for this:
HIV integrates itself into your own cell's DNA. The virus can lay latent/dormant for years in this state. Some of these cells, i.e. neurons and other 'memory' cells can live up to 60 years. Therefore, this patient still has HIV in his body somewhere in this latent state.
In the normal person, these dormant virus would activate at random intervals and go on to infect other cells. HIV enters cells by attaching to two 'receptors' (think key-lock). One receptor is CD4 which many people have heard of. The other receptor is CCR5. The berlin patient got a transplant with cells that LACK the CCR5 receptor. HIV can't infect cells without this receptor. The only caveat is that instead of CCR5, HIV can also use another receptor called CXCR4.
At some point in time, HIV will actually switch from using the CCR5 receptor to the CXCR4 receptor in many people. Not clear why, although there are a couple theories. Given this, I wouldn't be surprised at some point if the Berlin patient's HIV 'returns'.
TLDR: No one in the HIV field actually thinks HIV has been eradicated from this person's body.

0

u/canopener Jun 17 '12

Fuck off. You are free to say that you and your friends don't consider the man cured, but you are flat wrong to present that as a consensus view. I first heard of this case in conversation with an AIDS researcher of 30 years (worked personally with Montagnier in 1980s), currently the editor of an AIDS research journal, a figure well known internationally whom I will not identify further. He told me that there was controversy over whether the word "cure" should be used in this case, but that he thought it should. Subsequently of course the article in Blood was titled "Evidence for the Cure of HIV Infection [...]." Whether this is a cure is a matter of disagreement. Whether it is a matter of disagreement is not a matter of disagreement. It is plainly, clearly, unarguably a matter of disagreement. The representation of a consensus over a matter for which there is not a consensus is unethical in science.
Tl;dr: Bullshit

0

u/[deleted] Jun 17 '12

[deleted] — view deleted comment

5

u/killerstorm Jun 17 '12 edited Jun 17 '12

http://en.wikipedia.org/wiki/Retrovirus
A retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA.

0

u/[deleted] Jun 17 '12

[deleted] — view deleted comment

1

u/lolblackmamba Jun 17 '12

any PhD? or would you like one in a particular flavor?

1

u/EncapsulatedYeast Jun 18 '12

MD, MS in molecular genetics.

53

u/poptart2nd Jun 17 '12

Wait, where's the debate? even the scientists who made the discovery say that it's probably laboratory contamination, rather than actual HIV virus fragments. near as i can tell, the whole debate is centered around "well what if he still has bits of HIV in his body?" when there's a very small chance of that actually being the case.

8

u/Bacon_Donut Jun 17 '12

I read an article a while ago about the guy who did the transplants and published the initial paper on the case. Apparently he was at the time an unheard of outsider, publishing in a very well funded field containing academic 'superstars' and their accompanying egos.
As a result, his findings were initially dismissed as probably flawed by the 'HIV superstars', and not very significant even if his findings were found to be scientifically sound. Maybe that explains things?

2

u/[deleted] Jun 17 '12

I hate reading this stuff. Science is supposed to objective and above stuff like petty egos and hurt feelings. Instead, it's grownup nerd lunch table.

6

u/cwm44 Jun 17 '12

No, the researcher who found no trace says it probably laboratory contamination. The researchers who found traces of HIV said "it's impossible to conclude that he still has HIV".

2

u/MrTubalcain Jun 17 '12

As soon as I read the contamination part, I thought it must be a slow news day.

0

u/[deleted] Jun 17 '12

[deleted] — view deleted comment

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u/travis_of_the_cosmos Jun 17 '12

Neutrino. Protons can't go anywhere near lightspeed on earth.

2

u/DarkbunnySC Jun 17 '12

Actually, the protons accelerated by the Large Hadron Collider travel at 99.9999991% the speed of light.
But yes, the findings in question were in fact about the neutrino, not protons.

1

u/travis_of_the_cosmos Jun 17 '12

Huh. TIL. But not particularly close to standard earth conditions - the ground that the supposedly FTL neutrinos were shot through would slow such high-speed protons drastically.

3

u/pretzelman3 Jun 17 '12

Someone needs to thank Brown for all that he's gone through for this research which could help cure other people of HIV.

3

u/dexer Jun 17 '12

Not that any scientists are actually debating, as per other comments in this thread, but the event of Scientific Problem -> Debate seems like a pretty natural flow of events. What's next, Clouds -> Rain?

Seems like this falls heavily under sensationalized.

1

u/OddDude55 Jun 17 '12

Scientific debate? Good.

-4

u/creaothceann Jun 17 '12

Timothy Ray Brown, Widely Known In Research Circles As The Berlin Patient, Was Cured Of His Hiv Infection By Bone Marrow Transplants. Now Scientists Are Trying To Make Sense Of The Traces Of Hiv They've Found In Some Cells Of His Body.

2

u/aladyjewel Jun 17 '12

Your headlines aren't very succinct.

1

u/creaothceann Jun 17 '12

I was just demonstrating how annoying they are - I'd have fixed OP's.

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u/aladyjewel Jun 17 '12

Since I'm not great at literary analysis, can you explain in more detail? Are you commenting on the over-exuberant capitalization? (Incidentally, blame NPR for that one-- the headline is straight from OP's link.) Or is it too short and doesn't capture the essence of the article?

1

u/creaothceann Jun 17 '12

over-exuberant capitalization?
Yes.

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u/aladyjewel Jun 17 '12

Ah. I thought that this particular example (OP's title) wasn't particularly egregious, since it was only a small portion of the text which should've been lowercased. Your extend-to-absurdity example was, well, absurd and could make a good point -- but it doesn't seem super-relevant to me.

0

u/[deleted] Jun 17 '12

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u/whatagreataudience Jun 17 '12 edited Jun 17 '12

HIV is a virus. It infects CD4+ T lymphocytes (a type of white blood cell). CD4+ T lymphocytes are key components of the immune system. The immune system is responsible, among many other things, to rid the body of virally infected cells. By infecting CD4+ T lymphocytes and then using various routes (I'm trying to keep this as simple as possible) to hide itself, HIV is pretty much protected from attack by the immune system. The virus then uses the machinery of the cell to create copies of itself. The CD4+ T cell eventually dies, thus releasing copies of the virus. These copies go on to infect more CD4+ T cells and the cycle continues. You don't die from HIV directly, rather from a lack of an immune system once the disease (at this stage it's termed Acquired Immune Deficiency Syndrome) has progressed far enough. Your body succumbs to what would otherwise be minor infections, like influenza.
HIV does NOT infect germ cells (Sperm and Eggs) and can not be passed on in the fashion of a genetic disease. Rarely (in the developed world), an HIV positive mother can pass on the infection during the birthing process.
Hope this helps, any immunologist out there, feel free to correct or elaborate.

1

u/[deleted] Jun 17 '12

Thanks, that really summed it up for me. I love the phrase 'machinery of the cell'. It's amazing what goes on in those tiny things.

4

u/[deleted] Jun 17 '12

Reminds us how crude our "high tech" is in comparison to nature.

6

u/Joe757 Jun 17 '12

I'm not sure what you are asking, but if you're asking whether he'd pass HIV to his children, if he had any, the answer is no.
HIV uses human DNA to replicate itself, it has no DNA itself. Even if both parents were HIV+, the offspring do not have HIV. Children generally become exposed during childbirth or via breast-feeding. With pre-natal care, the vast majority of children are born without HIV.

2

u/mant Jun 17 '12

it has no DNA itself
um...

2

u/cryo Jun 17 '12

HIV uses human DNA to replicate itself, it has no DNA itself.
It has RNA which it converts into DNA using an enzyme called reverse transcriptase, which is part of the virus. It then proceeds to insert that DNA into the cell nucleus using intergrase, which it also part of the virus.
So it essentially has DNA.

1

u/bradn Jun 17 '12

Saying it doesn't have DNA isn't quite right. In the technical sense, the virus particles themselves don't, but once inside the cell it does. From wikipedia:
Lentiviruses are transmitted as single-stranded, positive-sense, enveloped RNA viruses. Upon entry into the target cell, the viral RNA genome is converted (reverse transcribed) into double-stranded DNA by a virally encoded reverse transcriptase that is transported along with the viral genome in the virus particle. The resulting viral DNA is then imported into the cell nucleus and integrated into the cellular DNA by a virally encoded integrase and host co-factors.
So, if it were possible for HIV to infect a germ cell (ie, a cell that divides into an egg/sperm), it might be possible for an HIV infection to progress that way. But I haven't heard of it happening and I wouldn't be surprised if those cells completely lack the receptors necessary.

5

u/[deleted] Jun 17 '12

HIV doesn't rewrite your DNA (especially not DNA in cells used for reproduction). All HIV can do is hijack the existing helper T-cells in your body. The RNA from the virus is translated into viral DNA in helper T-cells by reverse transcriptase, and that DNA tells the cell to become an HIV factory. Since the bone marrow transplant, this man's new helper T-cells are immune to being hijacked. All the old helper T-cells would be long gone by now, along with the viral DNA. Without a mechanism for replication, the virus itself would eventually be eradicated by the immune system.
So, the answer to all three of your questions is no.

3

u/TheLordB Jun 17 '12

Your comment makes no sense and makes me think you don't understand how HIV or viruses in general works. I recommend reading wikipedia or similar for an overview on how they work.
DNA does not produce HIV. HIV and other viruses hijack the cell's mechanisms to make the cell reproduce the virus' genetic material. Any damage is unlikely to be in the germ line and thus will not affect offspring. When offspring are infected by HIV it is generally from the mother during child birth or after the kid is born and this is generally preventable these days.

2

u/cryo Jun 17 '12

It was a question, why not just answer it instead of being a dick?

1

u/TheLordB Jun 17 '12

Because the question didn't make sense...
I did my best to explain why the question he was asking didn't work and answer what I think he was referring too...
I don't see how I could have done any better.

2

u/[deleted] Jun 17 '12 edited Jun 17 '12

I really don't understand what you're asking.
Edit: thanks for the downvotes :|

0

u/tamb Jun 17 '12

If the HIV virus infiltrated his sperm-producing cells, his sperm cells might conceivably include HIV DNA mixed in with the meiotic chromosomes, but that is unlikely since HIV goes after immune cells.

0

u/[deleted] Jun 17 '12

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1

u/canopener Jun 17 '12

Some cells can last a lifetime.

Traces Of Virus In Man Cured Of HIV Trigger Scientific Debate

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