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A potential cure for AIDS

It appears to be an excellent example of serendipity happening right in front of the prepared mind.
 
It is highly questionable if CCR5 non-expression alone is enough to provide full resistance.
 
Mm. This procedure is not a complete solution, unfortunately. There are a few limitations:

  • It will solve the problem if the patient's infection is limited to blood cells, but if the infection has spread to other tissues, replacing blood cells will not stop further propagation. ie: it may be useful in cases of HIV+, but not necessarily in cases of AIDS.
  • It will solve the problem if the strain is sensitive to CCR5 absence. If the strain is adapted to CCR5 absence, it will have no effect. Further: it's possible that after all this effort, the patient will be infected with a new strain of CCR5 adapted HIV anyway. This is also the criticism directed at prophylactic use of Selzentry.
  • Replacing bone marrow carries its own risk of fatality.
  • Good luck finding a match in the first place.
  • Bone marrow transplants - like all organ transplants - may require a lifetime of immunosuppression medications. ie: the solution to a disease that affects the immune system may be to defeat the immune system?
  • The CCR5 receptor *does* have a normal function. People without CCR5 receptor expression buy HIV vulnerability at a cost.
 
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Isn't there some evidence of inherited or emergent immunity to HIV/AIDS amongst some Ugandan women? Is this the CCR5 mutation, or something else?
 
volatile said:
Isn't there some evidence of inherited or emergent immunity to HIV/AIDS amongst some Ugandan women? Is this the CCR5 mutation, or something else?
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There are many examples of reduced vulnerability, but I'm unaware of proven total immunity. HIV has different strains.

These all involve mutated CCR12 or CCR5 receptors, as far as I know.
 
volatile said:
Isn't there some evidence of inherited or emergent immunity to HIV/AIDS amongst some Ugandan women? Is this the CCR5 mutation, or something else?
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The women were sex workers which appeared to have a strong CTL response to HIV and could maintain this response because of their high exposure to the virus. When they ceased working in the sex trade then they became overtly HIV+. Presumably they were infected but this was not detected by blood tests.
 
blutoski said:
Mm. This procedure is not a complete solution, unfortunately. There are a few limitations:

  • It will solve the problem if the patient's infection is limited to blood cells, but if the infection has spread to other tissues, replacing blood cells will not stop further propagation. ie: it may be useful in cases of HIV+, but not necessarily in cases of AIDS.
  • It will solve the problem if the strain is sensitive to CCR5 absence. If the strain is adapted to CCR5 absence, it will have no effect. Further: it's possible that after all this effort, the patient will be infected with a new strain of CCR5 adapted HIV anyway. This is also the criticism directed at prophylactic use of Selzentry.
  • Replacing bone marrow carries its own risk of fatality.
  • Good luck finding a match in the first place.
  • Bone marrow transplants - like all organ transplants - may require a lifetime of immunosuppression medications. ie: the solution to a disease that affects the immune system may be to defeat the immune system?
  • The CCR5 receptor *does* have a normal function. People without CCR5 receptor expression buy HIV vulnerability at a cost.
Click to expand...

600 days does seem to be a long period of remission though.

What function, what would the cost be, to someone without this CCR5 receptor. It seems there is a small set of the population who already have this mutation. How are they disadvantaged? The article mentions increased vulnerability to West Nile virus but is there something more substantial?

How common is one type of HIV (CCR5) vs the other, are there estimates along those lines?
 
jdp said:
600 days does seem to be a long period of remission though.

What function, what would the cost be, to someone without this CCR5 receptor. It seems there is a small set of the population who already have this mutation. How are they disadvantaged? The article mentions increased vulnerability to West Nile virus but is there something more substantial?

How common is one type of HIV (CCR5) vs the other, are there estimates along those lines?
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The purpose of CCR5 is an area of active study. One example (of many):

Impact of the CCR5 gene polymorphism on the survival of metastatic melanoma patients receiving immunotherapy.
Pubmed ID: 17909797

In that case, people with nonfunctional CCR5s had poorer outcomes during immunotherapy treatment for melanoma. In many of the other studies I quickly skimmed, CCR5 polymorphisms have no effect (examples there included coronary artery disease and Hep C).

As for the distribution of tropisms of HIV -- that's regionally dependent (similarly with HIV types).

So we don't really have a full handle on why one needs a CCR5 receptor, but it clearly matters sometimes. Vague, I know. But if you head over to Pubmed, there are nearly 5,000 papers that somehow touch on CCR5 -- lots of reading. :)
 
blutoski said:
There are many examples of reduced vulnerability, but I'm unaware of proven total immunity. HIV has different strains.

These all involve mutated CCR12 or CCR5 receptors, as far as I know.
Click to expand...

Capsid said:
The women were sex workers which appeared to have a strong CTL response to HIV and could maintain this response because of their high exposure to the virus. When they ceased working in the sex trade then they became overtly HIV+. Presumably they were infected but this was not detected by blood tests.
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Interesting - thanks both.

Capsid - what's "CTL response"? And how would their sex work affect it?
 
volatile said:
Interesting - thanks both.

Capsid - what's "CTL response"? And how would their sex work affect it?
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CTL = cytotoxic T lymphocyte which is a special immune cell that can target virus infected cells and kill them. The continued exposure to HIV through intercourse will cause the CTLs to maintain high numbers and activity that can deal with the infection and keep the virus load at a low level.
 
At 5% or so of the European population and not much better elsewhere except in a small Jewish population, there will be so few potential donors that match infected patients, even if the cost was manageable, this won't help many people. Years from now it might lead to some king of gene therapy where a virus could carry the CCR5 deletion gene into a new host. But that is a very very long way off.
 
jdp said:
600 days does seem to be a long period of remission though.

What function, what would the cost be, to someone without this CCR5 receptor. It seems there is a small set of the population who already have this mutation. How are they disadvantaged? The article mentions increased vulnerability to West Nile virus but is there something more substantial?...
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CCR5 deletion is hypothesized to have arisen in Europe because it provided some advantage to plague survivors. I'm not sure what the latest status of that hypothesis is however.
 
Wow, intereasting and amazing.

sound like that could help alot.
 
blutoski said:
On topic: [Not the cure for AIDS]
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I am not saure how to respond here.

If the patients walks from the hossital HIV- then it appears that this treatment *is* the cure.

It might not be risk-free, it might not be easily available, but it exists. As far as I am aware, that's a whole lot better than everything we had prior to this.

Bone marrow transplants are dangerous for patients.
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This has been brought up elsewhere, and I just don't understand why this should be an objection. How dangerous can it be compared to, picking an example purely at random here, dying from AIDS or leukaemia?

Bone marrow transplants are very expensive and not an option for many people living with this disease around the world.
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Doesn't make it any less of a cure, though. Right, so it might not purge HIV and AIDS from the face of hte earth within the next couple of days - but it still is a potential cure against it.

Does anybody know if the treatment has to happen the same way as with cancer? Would it be possible to supply a patient with the new cells without killing the old ones first, e.g.?

Somebody shut me up if this is just crazy, I am no expert at all, so may understanding of the process is probably terribly flawed ... but:

With leukaemia I have to kill the patients bone marrow first because it's cancerous and the cancer would spread again if it stayed, right?

Is that a problem with HIV, though? If I simply supplied the patient with immune bone marrow, wouldn't that go on to produce immune blood cells? I am not sure if that would be good enough to at least keep the virus under controll let alone remove it fully - it is simply not obvious to me that the therapy has to follow the same route in both cases.
 
The CCR5 mutation doesn't make a person totally immune to HIV, though it would innately immunize them to the bulk of HIV infections which use the CCR5 (which is often abbreviated to R5). There are HIV infections that can use the CXCR4 (often abbreviated to R4) receptor, if not both the R5 and X4 (either or) though rare, they do exist.

I should note the CCR5 mutation comes with a price -- people with the R5 mutation are virtually immune to most HIV strains, but are highly vulnerable to contracting West-Nile Virus -- which is usually rarely kills unless you're old or in bad shape. People with the R5 mutation are more likely to contract the disease, suffer more severe symptoms, and are more likely to die from the disease.

Additionally (I'm not sure why I should mention this, but from a purely biological and scientific perspective) if you're a methamphetamine user even if you have the R5 mutation... you can still get the disease. It turns out methamphetamine in one way or another (directly or through the chemical byproducts as it breaks down in the body) destroys the proteins that protect people with HIV immunity from the disease.


BTW: The CCR5 Delta 32 Mutation wasn't caused by an adaptation to the plague. It appears as if it was caused by smallpox or a smallpox-like virus.
 
skeptigirl said:
CCR5 deletion is hypothesized to have arisen in Europe because it provided some advantage to plague survivors. I'm not sure what the latest status of that hypothesis is however.
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I think I heard that somewhere before (even before this news). I was just wondering what the disadvantage might be if someone were to take this route as a treatment. Such as is increased susceptibility to West Nile, as an example, an actual problem.
 
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