RySerr21

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its a little pre mature to be declaring a cure for AIDS, but its definitely interesting. I'm gonna bring it in to work and see what the doc thinks about it.
 

JeetKuneDo

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This is really really interesting. Hopefully we can build from this.
 
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TooMuchResearch

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"Perhaps the most important caveat is just how risky bone marrow transplantation is: It’s given to cancer patients after other treatments fail, and it kills up to 30% of patients."

This part of the article really stands out for me. I'm assuming most of the 30% die from Graft Versus Host Disease, which is essentially the opposite of transplant rejection (or the exact same thing if you think of the newly transplanted immune system as the host and the body they are put into as the transplant).

Also, I'm not completely convinced that this guy's viral load will stay in the zero range. They gave him a transplant from a CCR5 chemokine receptor mutant. These mutant receptors are found in people that still get HIV but are called long term non-progressors because the HIV-infected individuals with these phenotype typically do not get AIDS. Unless they successfully killed off all of the infected CD4+ T cells, macrophages, dendritic cells, etc. that carry HIV, the virus still may be present at low/undetectable levels and could show up again.

Still a very cool article. Thanks for providing the link :)
 

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I work on a bone marrow transplant unit and the principle is sound, but the method they used wouldn't be a wide spread treatment. First of all finding allogenic donors isn't easy in itself, but finding allogenic donors that are both compatible and carry HIV resistance would be extremely difficult. (ie not many people would be matched) Plus, BMTs have alot of risk involved - the high dose chemo used to destroy the host marrow leaves the patient at high risk of death by treatment and/or organ damage as well as high risk for secondary cancers. Also even if the graft holds you can have complications like GVHD (graft versus host disease) or possibility of relapse of host tissue (thus providing fodder for HIV).

So it'll never be a "good" solution (unless someone comes up with a gentler way to destroy someone's marrow). But the case does offer the possibility for a "cure" for HIV (with risks). The next path I see is to better understand the genetics of HIV resistance. I'm not completely up to date, but the last time I read research on the topic is that the prevailing theory is that HIV resistance is linked to a altered membrane protein on T cells that prevents HIV from latching onto the cell. Now if the genetics is well understood you could harvest marrow from a patient, grow the cells in a dish, and do gene therapy to replace the wildtype membrane protein with the resistant strain. Then destroy the marrow in the patient and give him/her a gene augmented/altered autologous transplant. This doesn't get rid of the risks from the high dose chemo, but will reduce the risk of GVHD, minimize the need for immunosuppression, and get rid of the problem of finding matched HIV resistant donors.

But again, BMTs are very risky and given the effectiveness of most protease inhibitor cocktails I don't see it as a routine treatment. But alot of HIV positive people do get secondary lymphomas and leukemias because of their HIV, and I do see this as an exciting avenue for simultaneously treating their cancers as well as their HIV. Plus, while still very risky, BMT continues to make strides as they fine tune the drug regimens. It's legions better than in the 70s when everyone was dying from the chemo (VOD, tumor lysis, etc.) or being devoured to death by GVHD.

AIN'T MEDICINE COOL?
 
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tabrazinski

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I work on a bone marrow transplant unit and the principle is sound, but the method they used wouldn't be a wide spread treatment. First of all finding allogenic donors isn't easy in itself, but finding allogenic donors that are both compatible and carry HIV resistance would be extremely difficult. (ie not many people would be matched) Plus, BMTs have alot of risk involved - the high dose chemo used to destroy the host marrow leaves the patient at high risk of death by treatment and/or organ damage as well as high risk for secondary cancers. Also even if the graft holds you can have complications like GVHD (graft versus host disease) or possibility of relapse of host tissue (thus providing fodder for HIV).

So it'll never be a "good" solution (unless someone comes up with a gentler way to destroy someone's marrow). But the case does offer the possibility for a "cure" for HIV (with risks). The next path I see is to better understand the genetics of HIV resistance. I'm not completely up to date, but the last time I read research on the topic is that the prevailing theory is that HIV resistance is linked to a altered membrane protein on T cells that prevents HIV from latching onto the cell. Now if the genetics is well understood you could harvest marrow from a patient, grow the cells in a dish, and do gene therapy to replace the wildtype membrane protein with the resistant strain. Then destroy the marrow in the patient and give him/her a gene augmented/altered autologous transplant. This doesn't get rid of the risks from the high dose chemo, but will reduce the risk of GVHD, minimize the need for immunosuppression, and get rid of the problem of finding matched HIV resistant donors.

But again, BMTs are very risky and given the effectiveness of most protease inhibitor cocktails I don't see it as a routine treatment. But alot of HIV positive people do get secondary lymphomas and leukemias because of their HIV, and I do see this as an exciting avenue for simultaneously treating their cancers as well as their HIV. Plus, while still very risky, BMT continues to make strides as they fine tune the drug regimens. It's legions better than in the 70s when everyone was dying from the chemo (VOD, tumor lysis, etc.) or being devoured to death by GVHD.

AIN'T MEDICINE COOL?

yeah, you're totally right. also within the scientific community this isn't actually that surprising at all. they just replaced all of his cells with cells that don't have the CCR5 receptor so the virus can't infect cells. this mutation, the CCR5 delta-32, is present in less than 2% of the western european population (it is so high because it also protects from the plague), but is basically non-existent outside of a small fraction of europeans. even if we could somehow match people and transfer cells to people in places where HIV is most prevalent, those areas are endemic to lots of other diseases like TB and west nile...
 

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A long while back CNN posted a really encouraging article. It was gone within one day, but it proved extremely hopeful for AIDS patients. Lets hope this can be modified to help out a larger population.
 

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I too am somewhat skeptical that his viral load will permenantly remain at zero. But it's pretty cool nonetheless.


They can't prove a viral load of zero. HAART often causes patients to reach a viral load that is undetectable. That doesn't mean they are cured.
 

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My old roommate took a HIV class, and apparently there is a group of prostitutes in Africa which are immune to HIV, due to their enormous exposure to it. Apparently, they lose their immunity if they stop being exposed and then are re-exposed. He was kind of nuts, so I don't know how legit this is, has anyone heard of it?
 

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My old roommate took a HIV class, and apparently there is a group of prostitutes in Africa which are immune to HIV, due to their enormous exposure to it. Apparently, they lose their immunity if they stop being exposed and then are re-exposed. He was kind of nuts, so I don't know how legit this is, has anyone heard of it?
what the hell:laugh:
 
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mmmcdowe

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pazan

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This is definitely a small, but positive step for AIDS research. Thanks for the link.

I work in neuro, and this reminds me of a treatment for Multiple Sclerosis and Myasthena Gravis that's much safer than BMT. High dose cyclophosphamide is used to destroy the patient's mature immune system (WBC goes to 0), but spare immune cell progenitors in bone marrow, which "rebuild" the immune system after treatment is discontinued. It's promising as a cure for MS in a limited group of patients; in the most recent study something like 4 of 9 subjects had their MS stay in remission for 2 years (and counting).

http://archneur.ama-assn.org/cgi/content/full/65/8/1044
 

lainey234

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My old roommate took a HIV class, and apparently there is a group of prostitutes in Africa which are immune to HIV, due to their enormous exposure to it. Apparently, they lose their immunity if they stop being exposed and then are re-exposed. He was kind of nuts, so I don't know how legit this is, has anyone heard of it?

I took an immuno class last year taught by a professor who is really big into HIV research (she's on a few international boards and such). She basically shared the exact same story with us.

http://query.nytimes.com/gst/fullpage.html?sec=health&res=9801E1D9123FF930A35751C0A9669C8B63
 

Bacchus

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This is definitely a small, but positive step for AIDS research. Thanks for the link.

I work in neuro, and this reminds me of a treatment for Multiple Sclerosis and Myasthena Gravis that's much safer than BMT. High dose cyclophosphamide is used to destroy the patient's mature immune system (WBC goes to 0), but spare immune cell progenitors in bone marrow, which "rebuild" the immune system after treatment is discontinued. It's promising as a cure for MS in a limited group of patients; in the most recent study something like 4 of 9 subjects had their MS stay in remission for 2 years (and counting).

http://archneur.ama-assn.org/cgi/content/full/65/8/1044
That's good to hear, but I've had a family member in remission 10+ years using Avonex? Is this therapy promising to better or just another alternative?
 

GoldShadow

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My old roommate took a HIV class, and apparently there is a group of prostitutes in Africa which are immune to HIV, due to their enormous exposure to it. Apparently, they lose their immunity if they stop being exposed and then are re-exposed. He was kind of nuts, so I don't know how legit this is, has anyone heard of it?
It is true, like lainey said. I remember reading the actual paper but it was a while ago and I can't remember the details.

edit: found a link to the abstract if you're interested: http://www.ncbi.nlm.nih.gov/pubmed/18707157
 

RySerr21

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They can't prove a viral load of zero. HAART often causes patients to reach a viral load that is undetectable. That doesn't mean they are cured.

Yea but at least they know the reason it is undecetable. If those patients stopped taking their meds, their viral load would go up. The crazy part about this patient is that he doesnt take any HIV medication, and yet his viral load is undectable. Thats strange.
 

Vihsadas

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This is definitely a small, but positive step for AIDS research. Thanks for the link.

I work in neuro, and this reminds me of a treatment for Multiple Sclerosis and Myasthena Gravis that's much safer than BMT. High dose cyclophosphamide is used to destroy the patient's mature immune system (WBC goes to 0), but spare immune cell progenitors in bone marrow, which "rebuild" the immune system after treatment is discontinued. It's promising as a cure for MS in a limited group of patients; in the most recent study something like 4 of 9 subjects had their MS stay in remission for 2 years (and counting).

http://archneur.ama-assn.org/cgi/content/full/65/8/1044

Yeah, I've heard of this too. The physician that presented one of my classes with the autologous BM transplant for MS called it "curative". That's an earth-shattering word to be heard in the context of MS, or any other autoimmune suspected neurological disorder.
What I'm waiting for is: Autologous BM harvest and isolation of HSCs or pluripotent cells (really any progenitor cell-line not susceptible to HIV), knock-in of CCR5 resistence gene, in vitro differentiation to HSCs, and then re-implatation of newly created CCR5 mutant autologous cells. Non immunogenic, and HIV resistant.

Now, I guess the issue that comes up is risk vs. reward. Even if we could do what I suggested, the risk vs. reward of a BM transplant far outweighs that of ARV treatment. Good ARV treatment has essentially the same effect as the BM transplant, minus the re-proliferation of the virus after treatment is stopped. Then again, ARVs don't have a 30% chance of killing you...

Yea but at least they know the reason it is undecetable. If those patients stopped taking their meds, their viral load would go up. The crazy part about this patient is that he doesnt take any HIV medication, and yet his viral load is undectable. Thats strange.

Well it's definitely cool, but I wouldn't call it strange. ARVs prevent HIV from proliferating, as does this mutation. I gues the difference is that the mutation is permanent. :p

They can't prove a viral load of zero. HAART often causes patients to reach a viral load that is undetectable. That doesn't mean they are cured.

I agree. HIV is a retrovirus, so even if you completely eradicate the viral particle load, couldn't HIV have inserted itself into the genome of some CCR5 positive cell in a place that could become transcribed in the future?
 
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