File this under "Whoa thats cool! But its not really a realistic solution for the AIDS pandemic."
It sounds like a cruel joke, but HIV patients have increased odds of developing leukemias and lymphomas. These cancers arent necessarily directly related to HIV (there is no reason to think HIV-1 is directly causing the cancer, like HPV and cervical cancer), but because of this relationship, an obvious question comes up: How the hell do you treat someone with leukemia and HIV?
A hospital in Germany tried something I cant believe no one has tried before... They gave a patient regular chemotherapy to kill off the cancerous cells (which also killed off most of the cells infected with HIV). They then replaced his bone barrow with marrow from a homozygous delta-32 donor-- A donor from a group of people who totally lack one of the co-receptors HIV-1 needs to get into your cells (pic from article).
So the physicians killed *most* of the patients HIV-1 infected cells, and replaced them with uninfectable cells. So even though there might be some infected cells left, the viral progeny had no place to go.
600 days later, the patient is doing great. 'Functionally cured' of HIV-1. They cant find the viruses anywhere.
Of course,"caveats are legion" (lol)-- 30% of patients die from the chemo/transplant. This treatment is even more expensive and intensive than anti-retrovirals-- It would be impossible to implement in the areas that need an AIDS cure the worst (Africa). But the success of this patient is giving hope to people like David Baltimore, who is currently trying to cure AIDS by genetically engineering individuals own white blood cells to not express CCR5, or to express the right antibodies... but even if Baltimores therapies are less invasive than a complete bone marrow transplant, it still takes some balls to think personalized genetic engineering is a viable HIV treatment in Africa...
Oh well. Its still cool. Appreciate it for being cool. But right now, with todays technologies, its not a solution to the worlds HIV-1 pandemic.
I have the Delta32 CCR5 mutation. I've known for 5 years and have been trying to find someone interested in testing a bone marrow procedure. I've always felt knowing I have the mutation would allow me to help at least one HIV patient. Are there any physicians looking for donors with this mutation?
Yes I would be very interested. But where could the BMT be done? I would be willing to cover all costs and expenses. Please let me know via email.
# 13 here. Are you a physician? How can I contact you?
No, this treatment is certainly not do-able for the entirety of the HIV infected population of Africa (or anywhere else for that matter). HOWEVER, it does shine a ray of hope onto what had recently been a series of spectacularly disappointing failures for what had been considered some promising treatments. If it is possible to "genetically engineer" infected individuals -- and do so with a single shot -- that's certainly a very do-able prospect, and one need look no further than the world efforts to eradicate smallpox and severely curb polio as examples.
blood-brain barrier? Doesn't HIV sometimes end up chillin' in the brain? If so, how do you get it out with chemo/bmt? Seems that there should still be places for it to chill out?
Whoa, indeed! That's one way to flush out one of HIV's hiding spots ...
I thought I recalled something like this being done back in the mid-90s, which had the unfortunate instance of being one of those cases where the patient died anyways, so "more research". However, google isn't helping me with finding confirmation of that ancient memory.
Wow! Even though this isn't something that could be done, yet, on a large scale it sounds like a much safer and sane alternative than the previously tried experiment of transplanting bone marrow from baboons.
M G Michaels and others. Transplantation 78(11): 1582-1589, December 15, 2004.
I recall something like this too. But didn't they use baboon bone marrow or something? Ostensibly baboons are immune to SIV/HIV. The experiment was a failure, however.
Anyone ever thought of using a retrovirus to target the CCR5 gene to insert a stop codon?
Joe Shelby, there's a 1989 case mentioned in the WSJ article that ERV links to where they don't know if the donor had the CCR5 immunity since that wasn't discovered yet.
This was the premise of the 1995 movie:
My Brother's Keeper with John Lithgow who played Two twin brothers, one of which was HIV positive.
The movie deals with their attempt to get their Health Insurance to pay for a bone marrow transplant using the healthy twin as a doner to cure HIV.
Doesnt hiv start using cxcr4 in chronically infected individuals? So why has this worked at all?
I think this patient just used up the entire world supply of serendipity. "Oh, yeah, about curing your leukemia. We did that and we seem to have cured your AIDS as well. Hope you don't mind."
The article says the individual is "still recovering" which, given the rate of complications with this procedure, may not necessarily equate with "doing great." The presence of HIV-specific T cells with delta32 might indicate if there's still virus around, don't know if they've looked.
Thanks for writing about this. I saw the article and wondered what it means for other HIV+ patients in rich countries -- whether they'll be lining up to start bone-marrow Facebook groups.
@dee - newer articles point out that this guy had CXR4 strains, as well, and they're now looking to see if something about the homozygous delta-32 folk that they're missing that entry point, as well. I did a review last night via google scholar and found one vaccination trial that only identified 2 delta-32 persons who seroconverted out of 15,000 participants (every sero-converter had been tested for this mutation), making a total of 8 known in the literature (Sheppard HW, Celum C, Michael NL, O'Brien S, Dean M, Carrington M, Dondero D, Buchbinder SP: HIV-1 Infection in Individuals With the CCR5-Î32/Î32 Genotype: Acquisition of Syncytium-Inducing Virus at Seroconversion.).
That's from 2002, but still implies that the rate of seroconversion among this 1% of populations of European decent contracts HIV at an extremely low level, and there are a number of more recent articles out explaining how, while sometimes more "fit," the CXR4/SI variants are less successful and less likely to occur as initial strains at time of seroconversion. Abbie would definitely be the better person to explain how/why!
@Jared - they can't do an insertion for the codon b/c this mutation is a deletion of 32 base-pairs (the Î32 bit), not an insertion of anything. I think that limits the possibilities, though new drugs are still coming onto the market mimicking the effect.
Anyway, late to the thread....