Personalized HIV therapy within reach?

Lots of people have been emailing me about this article, currently rotating through the usual science news outlets:

Science Daily
New Scientist
WIRED
Slashdot

*sigh*

Look, guys, I am obnoxiously optimistic about the future of HIV/AIDS. I have no doubts about our ability to one day make HIV/AIDS a distant nightmare, like polio or the plague.

And I also have no qualms with the paper these articles are based on, Establishment of HIV-1 resistance in CD4(+) T cells by genome editing using zinc-finger nucleases. Its neat! Yay!

But let me dump a big bucket of ice cold realism on the press release that spawned those ‘science journalism’ articles: This research is completely impractical in The Real World, and it sure as hell doesnt “Put Personalized HIV Therapy Within Reach”. Giving the general public that impression is deceptive and mean.

Again, I want to make it clear that I dont see anything ‘wrong’ with this paper. Its made up of good science and good ideas. My problem is the way its been ‘framed’ (as usual), so lets just look at the paper and its implications without spin.

Basics of HIV-1– It needs two receptors to infect your cells:
1– CD4
2– CXCR4 OR CCR5

You all might have heard of individuals who are naturally resistant to HIV-1 infection because they dont have a functional CCR5 gene (CCR5-Delta32). These people have no obvious deformities or abnormalities, so evidently you can live a pretty normal without CCR5.

However, most of us do have a functional CCR5. So we are totally screwed, right? Maybe not! This paper outlines some experiments done in mice born without an adaptive immune system who were injected with human T-cells that had been treated with a gene-therapy vector to screw up the T-cells CCR5 genes. The end effect is that the T-cells in these mice dont have functional CCR5s. When these mice were challenged with HIV, their modified human T-cells survived longer, and their viral loads were lower!

So, theoretically, one day researchers could take some T-cells from you, modify them a bit with gene therapy, inject them back into you, and then you would be like a delta-32! No CCR5, harder to get HIV! Or, if you were already infected with HIV, you might be able to hang on to your T-cells longer, thus delay the onset of AIDS.

WHOO!! Personalized HIV Therapy Within Reach!

… Not exactly.

Just to point out the obvious, this experiment has only been done in mice. Cell lines < animal models < non-human primate models < human therapy. A mouse system (especially when mice arent susceptible to HIV-1 infection without some tricks, like they used in this paper) is a far cry from a human clinical trial. These guys still have a loooong way to go to reach a workable therapy.

And, there is a major problem with 'just getting rid of CCR5'... CXCR4. Because HIV-1 can evolve to use CXCR4 instead of CCR5, 'just getting rid of CCR5' would be like closing your front door to keep a zombie outside... while leaving the back door wide open. It might take the zombie a minute, but hes gonna figure it out and feast on your brains.

But lets ignore all that. Lets pretend that human clinical trials go perfectly.

Lets pretend that for some reason, HIV-1 doesnt evolve around CCR5 to CXCR4.

How the hell is this ‘therapy’ going to help the people who need help the most?

Theyre going to take this treatment to rural Africa?

Really?

Ya they dont have reliable electricity or running water, but gene therapy, thats doable.

“Personalized HIV Therapy Within Reach” of people who could afford this kind of therapy. People in the US/Europe who can afford anti-retrovirals in the first place.

The people who need this therapy couldnt get it, and the people who could get it, dont need it.

UGH!

Im just so annoyed and so frustrated.

Just let science stand on its own. Appreciate a good idea and a well designed experiment. But this kind of patronizing PR is shameful.

Comments

  1. #1 Paul Lundgren
    July 3, 2008

    You wouldn’t happen to be a fan of Keith Olbermann, would you? You certainly have the same affinity for calling BS when you see it.

    Excellent analysis.

  2. #2 becca
    July 3, 2008

    Great post!
    I particularly love the zombie analogy!

  3. #3 Blake Stacey
    July 3, 2008

    “All the news that fits, we print”: it’s not the truth that matters, but rather the story which is most easily told. Affluent Americans care about a particular kind of possible treatment for HIV, so any scientific discovery about HIV will be described as the precursor to that treatment. Likewise, our culture cares about whether sexual orientation is innate or learned (quite possibly a false dichotomy, but never mind), so any result about brain-scanning people of different orientations will magically become “the most compelling evidence yet that being gay or straight is a biologically fixed trait“. Damn the actual science, full speed ahead!

  4. #4 Morgan Price
    July 3, 2008

    In principle, you do deliver the zinc-finger nuclease with an engineered virus, without taking the T-cells out and putting them back in. So, just maybe, someday in the distant future, something like this will work for people who don’t have electricity.

  5. #5 Mind Body Shop
    July 3, 2008

    After a year in therapy my psychiatrist said to me, “Maybe life isn’t for everyone.

  6. #6 Optimus Primate
    July 3, 2008

    That’s a really nice explanation and all, but we all know the
    real reason
    this’ll never work.

  7. #7 Optimus Primate
    July 3, 2008

    And just for the record, I did that funky line break on purpose.

    Yeah, that’s the ticket.

  8. #8 Sili
    July 4, 2008

    I guess it’s a good thing that this is the first I hear of this ‘news’. Commendably clear, as always.

    And congrats on the BadScience link.

  9. #9 Teek
    July 4, 2008

    cracking analysis. this is rather typical of the mindset surrounding HIV/AIDS: potentially interesting (but ages away from clinical application) biochemical interventions, which are usually expensive, get far more attention (more funding,higher profile publications, more press coverage etc) than measures aimed at prevention. Considering the vast majority of those infected with HIV (i.e. in Africa/S.E. Asia) contract the virus by sexual contact, the latter may have a greater impact in reducing the epidemic – but North American AIDS victims can afford gene therapy-type treatments, so their govts will pour money into research for this.

    grrr…

  10. #10 dvizard
    July 4, 2008

    #9: It’s not just HIV … In any kind of journalism about something vaguely biologically relevant, they never miss to write the line about how “this findings might be fundamental to new medical therapies of “. It gets me kind of frustrated, but it’s a result of nowaday’s public disrespect of basic research. Everyone wants TEH KILL0R THERAPIES now, but anything not leading directly to immediate cure of millions of people is a waste of money and most likely un-ethical and whatnot. Case in point, the recent Swiss court decision in the ETH/Uni monkey experiment case…

  11. #11 dvizard
    July 4, 2008

    Should have been
    “therapies of “.

  12. #12 NP
    July 5, 2008

    Even if a gene-based therapy such as this one were to be approved by the FDA after all the clinical trials, the issue of actually paying for the treatment would not only be relevant in Africa, but the United States as well. Antiretroviral drugs are already very expensive in the United States, and so we can probably expect any gene therapies to cost even more.

  13. #13 Kayleene
    July 5, 2008

    i wonder why there is still no cure for this disease.

  14. #14 Paul Lundgren
    July 6, 2008

    @Kayleene #13.

    I’m going to assume your question is not rhetorical. Since I’m not a virology specialist, I’m not qualified to answer that questions beyond this: It’s massively complicated beyond the point of the understanding of people trained in the field all of their adult lives. They’ll figure it out eventually, or at least lay the ground work for those who do, but viruses aren’t exactly as easy to fend off as a bacterium.

    Look at it this way: we still can’t “cure” the common cold or influenza once people have it, can we?

  15. #15 Felstatsu
    July 7, 2008

    @Kayleene,

    I’m not a virologist either, but basically HIV is a highly mutable virus and as such there is little ability to vaccinate against it since a vaccine would need to cover all the present versions as well as all the possible future variations on the virus. Beyond that there is also the fact that HIV likes to hide and is good at it so some immune systems in people can only see one part or another part of it, and so a vaccine would be immeasurably complicated to make with our current level of medical technology. Wikipedia “Virus structure” and look at the information about enveloped viruses, this covers how HIV and the flu hide.

    As for curing it, we hit the same problems that we have for preventing it. HIV hits the immune system so the body is less able to do anything about it when the virus is actually recognized as an invader by the immune system. I’ve also heard HIV iss hardy enough that something like an anti-biotic would have to be potent enough to basically kill the person who takes it.

    While I’m not sure it HIV does this, I believe some viruses are able to put up very effective protein barriers to protect themselves from hostile environments. Instead of asking why we don’t have a cure yet, it would be better to look for all the diseases caused by viruses we have cured, because as far as I know even the things we have vaccines for we can’t actually “cure” yet if someone gets infected before getting vaccinated. It’s possible that it has happened, but if it has it’s outside of my realm of knowledge, so the best I can say is that as far as my knowledge goes we have not “cured” any viral disease in someone infected by it.

  16. #16 Torbj�rn Larsson, OM
    July 7, 2008

    I’ve also heard HIV iss hardy enough that something like an anti-biotic would have to be potent enough to basically kill the person who takes it.

    Technically an antibiotic only works on cellular life like bacterias. Originally it was only referring to inhibitors of bacterias. (Viruses wasn’t considered life at the time the terms solidified, I believe.)

    So if you ask your drug store for an antibiotic you won’t be cured. Ask for an antiviral instead.

    It’s possible that it has happened, but if it has it’s outside of my realm of knowledge, so the best I can say is that as far as my knowledge goes we have not “cured” any viral disease in someone infected by it.

    Depends what you mean by “cure”. Certainly people have been able to help the natural immune system or antivirals along. For example, rabies can be treated by post-exposure prophylaxis (including vaccination). And they saved one unvaccinated rabies patient by inducing a coma (and a cocktail of antivirals and probably vaccine) to alleviate the virus’ effects on its behavior.

  17. #17 Xavier
    July 16, 2008

    In hope of injecting a little optimism I would suggest that, should an ex vivo T-cell treatment become available, the discipline of biomedical nanotechnology might be able to provide an economical delivery system for the therapy.

    Systems that take blood and separate specific cells from the mix (usually leucocytes or bacteria) for the purposes of diagnostics are in development in the form of sealed, single-use ‘lab-on-a-chip’ devices. Reworking such a system to specifically separate out T-cells and allow them to be treated with ZFNs, or whatever, is not only viable but potentially inexpensive.

    The devices are expected to be made using similar processes to computer chips – though with less complexity – so could be very cheap to make (less than $1 each) if large-scale production was required. Single use items with all reagents sealed inside during manufacture eliminates many safety issues and tiny amounts of power and reagent are needed as most of the operation is carried out at a micro scale. An ordinary battery could provide all the power needed for hundreds of devices. Up-scaling to give the device access to a significant proportion of the T-cells (possibly by plumbing the device into the circulatory system for a few hours) would still be a challenge, but requires no breakthrough technology.

    If the will is there – that is to say that the treatment really works so well that it might become cheaper to treat than to not-treat – then it can surely be made to work more cheaply than a years worth of antiretrovirals and once the technology and the market is in place it is quite conceivable that it will become cheap enough to deploy worldwide.

    I don’t know of anything of this type that has been tried, but between kidney dialysis, the cell sorters in haematology labs, the platelet harvesters in blood transfusion labs and the lab-on-a-chip devices, all the pieces are in place. It just needs a (large) bunch of production engineers and a wad of start-up cash (oh, and a one-shot treatment that will work) and we can make it work.

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