Hard Light Productions Forums
Off-Topic Discussion => General Discussion => Topic started by: General Battuta on December 14, 2010, 09:41:41 am
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Only once, and in one patient, and it was three years ago, but it appears that the patient has not relapsed so WTF, let's talk about it.
Doctors in Berlin believe that transplanting marrow from a CCR-5 negative individual into a patient with HIV cured not only his leukemia but his HIV. Stem cells from the CCR-5 negative dude replaced the patient's immune cells.
HIV uses the CCR-5 receptor as a way into cells, and it's long been known that people who lack the CCR-5 receptor (technically called CCR-5 delta 32 homozygosity, and found mostly in Scandinavia) are largely immune to HIV but otherwise healthy.
The treatment process used for this patient's leukemia, including the marrow transplants that cured his HIV, was incredibly grueling. But future therapies using stem cells from delta 32 homozygous donors might carry a lower risk of killing or debilitating the patient.
More here. (http://www.aidsmap.com/page/1577949/?r=1)
If you want to be cynical about it, the possibility remains that CXCR4-targeting HIV strains will emerge in this patient, or in the population at large if the therapy becomes more widely used. CXCR4 is another receptor often targeted by HIV.
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does this "cure" completely eliminate the virus to the point where it can no longer transmit the virus or does it make the patient a carrier who themselves does not suffer any further ill effects? also it must be noted that bone marrow transplants are usually a pretty brutal ordeal for both doner and recipient and are as expensive as they are painful. it sounds like this cure would be ridiculously expensive in places like africa where aids is a real problem. id really rather see better dispersal of aids medications to such places rather than see super-expensive cure options magically pop up. same kinda thing happens with malaria. we have drugs to help the disease, but distribution to the 3rd world is either lax or non-existant, or worse controlled by warlords as a means to maintain power.
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The virus is undetectable to any test performed on the patient so far, but that doesn't mean it's not present. HIV is notorious for going to ground in difficult-to-sample organs. If I were this guy I wouldn't be going to any orgies quite yet.
The brutality of marrow transports is indeed noted in the original post.
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I remember reading about/using this when I did a little AIDS research paper in freshman year. Surprisingly nobody, not even the professor, knew about it.
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I had wondered in the past why leukaemia treatments that basically consist of wiping out the immune system and then replacing it via transplants didn't work against AIDS.
Okay with the immune system dead there's nothing to scavenge up the HIV virus that isn't in the white blood cells but wouldn't a course of antivirals help there?
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I thought the anti-virals for aids were pretty brutal themselves
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Marrow transplants are difficult and easily lead to complications. It's questionable if you satisfy the Do No Harm vs Beneficence principle here.
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Marrow transplants are difficult and easily lead to complications. It's questionable if you satisfy the Do No Harm vs Beneficence principle here.
Third to last paragraph, first post!
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Because stem cell transplants will magically be much safer when you're trying to transplant an entire immune system. Gene therapy holds some promise, but that's a long-shot to get working, and not news in any way.
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I'm optimistic that future therapies might carry a lower risk.
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Just advocating for the devil. If any treatment works, I'd be as pleased as anyone.
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Marrow transplants are difficult and easily lead to complications. It's questionable if you satisfy the Do No Harm vs Beneficence principle here.
Third to last paragraph, first post!
Marrow transplant is not foolproof. At best, this "cure" is only useful to those who already need a marrow transplant, in which case the larger concern is whether or not the primary illness will be treated. Presence or absence of the receptors isn't even a secondary concern. Eventually, HIV/AIDS will help kill you.
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What?
At least in this case study, the guy's AIDS went into remission after he got new TH cells that lacked the receptor. After a generation turnover, the resident HIV would have serious issues keeping itself in the body except for the pockets of other tissues it could infect.
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Marrow transplants are difficult and easily lead to complications. It's questionable if you satisfy the Do No Harm vs Beneficence principle here.
Third to last paragraph, first post!
Marrow transplant is not foolproof. At best, this "cure" is only useful to those who already need a marrow transplant, in which case the larger concern is whether or not the primary illness will be treated. Presence or absence of the receptors isn't even a secondary concern. Eventually, HIV/AIDS will help kill you.
oh baldercocks
Third to last paragraph, first post, why are you restating what was said in the OP?
In fact further tonguelashing for not reading the article: presence or absence of the receptors is a primary concern because with them gone the HIV infection is apparently completely cured. Apparently. If appearances are true, it is gone from his body (but they may not be; HIV is capable of lurking in reservoirs as was, again, already clearly stated in this thread). His leukemia treatment was also successful but far more grueling and costly.
HIV/AIDS can't help kill you if it's gone. If therapies using delta 32 homozygous stem cell transplant can be devised without the impact of marrow transplant, it may provide a less destructive way to cure HIV in patients, if the virus does not develop resistance by switching receptors.
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It's more complicated then simply sticking the stem cells in a guy's thigh bone and hoping that his AIDS will go away. I see a couple of things that are wrong with this:
http://en.wikipedia.org/wiki/Graft-versus-host_disease: You're taking someone else's immune system and plopping it into your own body. Especially since you're not replacing the entire marrow, you can expect a lot of potential fighting between the immune systems as they mutually reject each other.
If TH cells of the host and the transplant decide to co-exist nicely, it'll likely only confer resistance, and not outright elimination of the HIV virus. Sure you won't be dead as quickly from having no immune system, but you'll be a carrier likely in a perpetually weakened state. Also, because you carry the new receptor along with a huge HIV reservoir, you're a walking selection tank to breed out HIV strains that will be able to use the new receptor.
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All discussed in the article.
Seriously if people don't start reading the OP and the linked article I may blow a gasket. I don't want to spend time answering 'objections' that are already settled in reality.
But here, because I am a ball of rage
You're taking someone else's immune system and plopping it into your own body. Especially since you're not replacing the entire marrow, you can expect a lot of potential fighting between the immune systems as they mutually reject each other.
See the article. Massive immunosuppression is part of why the marrow transplant was so grueling for the patient. That's how it was handled here. Better methods will be required if this therapy is to be made more accessible.
If TH cells of the host and the transplant decide to co-exist nicely, it'll likely only confer resistance, and not outright elimination of the HIV virus.
Read the thread, see the answer.
but you'll be a carrier likely in a perpetually weakened state. Also, because you carry the new receptor along with a huge HIV reservoir, you're a walking selection tank to breed out HIV strains that will be able to use the new receptor.
There is currently no evidence that this man is a huge HIV reservoir. Please review the posts in this thread, or the article, both of which explicitly state the current information we have on how much HIV remains in this guy's body.
The reason this is exciting is because it does not appear to have fought the disease to a standstill, it appears to have eradicated it. As has been stated more than once now, appearances can be deceiving.
The selection issue was also brought up in the first post.
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Calm down. You're talking about marrow replacement. I'm talking about stem cell injection.
The point I'm making is that all the problems with marrow replacement don't go away simply by citing stem cells as a solution.
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There are obviously a vast number of obstacles left to an effective, let alone affordable, cure. But if peripheral source stem cells from individuals without this receptor can be accumulated, that's - maybe - a first step.
In this case, the new immune cells lacking the receptor completely replaced the old ones in the patient's body. That suggests that partial replacement won't be a problem - except that in this case, radiation and chemo were required to wipe out the original immune system. That's messy.
We need to be certain that the virus is totally eradicated before we can figure out exactly how close to a miracle cure this is.
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Is 100% eradication absolutely necessary? If you can't find the virus in the guy's blood, then it's not actively replicating, ergo, not actively killing any immune cells. Suppression is more than enough to save a guy's life (though transmission of infection remains a distinct possibility). Of course, the suppression this guy got might be temporary, even though it has lasted 3 years. Then again, 3 years isn't much, since normal disease progression can have HIV take 10 years or so before symptoms appear.
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Yeah, it's the transmission issue. And if it remains in a reservoir in a hard-to-sample organ it could relapse later, especially if the CXCR receptor variant emerged.
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ITT: people who would've looked at the Wright flyer and said "bah, but it can't cross the ocean or go over mountains. Why get excited?"
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I'm not sure that's a non-negligible possibility. If there's no virus in the blood (well, then again, "no virus" just means too few for our techniques to pick up), it's pretty certain that no tissues have actively replicating viruses in them. Exception might be HIV in the CNS that can't cross the blood/brain barrier, but if those can't get out, they're not transmissible unless you start leaking cerebrospinal fluid etc. into people's cuts.
Without active replication, there's no selection. Without selection, it'd take pretty long for a new strain to emerge.
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I'm not sure that's a non-negligible possibility. If there's no virus in the blood (well, then again, "no virus" just means too few for our techniques to pick up), it's pretty certain that no tissues have actively replicating viruses in them. Exception might be HIV in the CNS that can't cross the blood/brain barrier, but if those can't get out, they're not transmissible unless you start leaking cerebrospinal fluid etc. into people's cuts.
Without active replication, there's no selection. Without selection, it'd take pretty long for a new strain to emerge.
I want to agree, since it'd be a dream scenario.
They seem to be leaning that way. I hope they're right.
Nevertheless HIV remained undetectable by both viral load testing (RNA) and tests for viral DNA within cells, and HIV antibody levels declined to the point that the patient has no antibody reactivity to HIV core antibodies, and only very low levels of antibodies to the HIV envelope proteins.
Seventeen months after the transplant the patient developed a neurological condition, which required a brain biopsy and lumbar puncture to sample the cerebrospinal fluid for diagnostic purposes. HIV was also undetectable in the brain and the CSF.
An additional indication that HIV is not present lies in the fact that the patient’s CD4 cells are vulnerable to infection with virus that targets the CXCR4 receptor. If any virus with this preference was still present, the researchers argue, it would be able to swiftly infect the large population of memory CD4 cells that has emerged.
There were CXCR4 viruses present before the marrow transplant, and I think they're the biggest risk factor, but
Before the treatment though the patient had low levels of the CXCR4 virus but after the treatment this type of HIV could not be detected either which Hütter called "very surprising".
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Aren't umbilical cords chock-full of stem cells?
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That is one possible method for gathering the necessary stemcells, yeah.
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Aren't umbilical cords chock-full of stem cells?
The issue with that is umbilical cord means babies which is a tetchy subject at best
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The current main source of stem cells is discarded embryos, which is a fair bit worse than umbilical cords.
Of course, there's research to tease differentiated cells back into stem cells, but so far those are limited by various problems and imperfections.
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Aren't umbilical cords chock-full of stem cells?
The issue with that is umbilical cord means babies which is a tetchy subject at best
Nah, umbilical cords are fine - there's not much controversy that I know of about harvesting them, since they're usually just discarded anyway.
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This guy had AIDS AND Leukaemia? Poor unlucky bastard. I mean in the end it seems to have turned out well for him but breaking the news to him about the second one of those must have been pretty uncomfortable. :p
Seventeen months after the transplant the patient developed a neurological condition, which required a brain biopsy and lumbar puncture to sample the cerebrospinal fluid for diagnostic purposes.
The neurological problem led to temporary blindness and memory problems. Brown is still undergoing physiotherapy to help restore his coordination and gait, as well as speech therapy.
Seriously unlucky. They don't say if the condition was related to either of the diseases. Cause if it was a third, unrelated condition.....
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His misfortune is a boon to the scientific community, though - that brain biopsy has to be valuable for figuring out if there was a latent HIV reservoir there. (I believe that does happen.)
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I don't know, the guy was cured of both of them, that screams lucky to me.
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I know, but at the time he got the second diagnosis..... :p
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I knew about this. I actually asked a professor about the theory concerning total immune replacement with altered chemokine receptors back in 2006. His answer, and I quote: With the current antivirals available, the risks of replacing an immune system to cure the virus far outweigh the potential cures.
It is definitely interesting that it actually worked in practice (to be honest, I'm a little surprised that the doctors in question are surprised after having found the chemokine mutation), but it's not entirely unexpected and definitely not a practical cure. For one, he shouldn't actually be cured of the virus itself - altering the chemokine prevents HIV from infiltrating T cells, but it doesn't contribute to efficacy in clearing viral load from the bloodstream. It DOES allow the immune system to catch up to the virus though, which in this case may have (this is surprising) allowed the immune system to actually clear the virus. Important distinction: this treatment didn't cure his HIV infection - it slowed the virus enough to allow his immune system to do it (apparently). However, considering the rate at which HIV mutates (dozens to hundreds of viral variants can be found in single patients after years of infection), it's a pretty safe bet that his HIV infection will probably eventually return - though with hefty doses of antiretrovirals and a good bit of luck, he may not relapse. Only time will tell. Part of the reason that HIV is such a nasty virus is because it is so good at evading the immune system and the antibody-mediated immune response in particular.
Anyway, I wouldn't jump up and down on this one too much. This is a case of really good luck combined with excellent medical care. Immune replacement therapies are so risky that they aren't an option for the majority of HIV infections, especially considering how good today's antiretrovirals are.
One option, as someone suggested, is to develop stem cell therapies whereby the immune system is not replaced but gains the ability to produce CCR5- T cells... in which case, the patient would still be infected with HIV and able to transmit it, but would not progress to AIDS and therefore have higher survivability. But that's a long, long way off... and there are other chemokine receptors that permit the virus to gain entry.
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Yeah, but the weird thing is that the variants of the virus which go for those other receptors were present before the therapy but also died. What up with that?
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Yeah, but the weird thing is that the variants of the virus which go for those other receptors were present before the therapy but also died. What up with that?
Maybe chemokine receptors use transcription/RNA splicing to create their various iterations. I wonder if the researchers ran an amino acid sequence of all this patients' chemokine receptors?
The other option is that if the alternate chemokine receptor transport mechanism isn't as efficient, the larger pool of available T cells essentially caught up and cleared those HIV variants too.
I would imagine that they're in the process of sequencing the donor genome entirely. I certainly would be, at this point.