In my earlier post about HIV therapy (a post I strongly recommend), I wrote, "After entering a cell (never mind how for now), HIV needs to find a way to makes copies of itself, which requires DNA." Because of some recently released data, it's time to look at how HIV enters the cell, and to expand a bit on the biology of HIV infection (but this is really a "Part II" so please refer to the above-linked post, even though this should stand on its own). This will also allow us another glimpse into how real science works. proceeding from observation, though hypothesis, and hypothesis testing.
Once again, as in all of my science-y posts, please forgive any oversimplification.
Observation
It has been observed that HIV requires a "lock-and-key" mechanism to bind to and enter human cells. The key is the HIV gp120 complex on the HIV envelope. The lock is the human CD4 receptor on certain human white blood cells, but this lock requires a little help to engage. Forming a proper lock-and-key fit requires the CCR5 or the CXCR4 receptor in the human cell membrane.
It has been further observed that some people are rather resistant to HIV infection, and that these people have a mutation in the CCR5 gene that doesn't allow it to appear on the cell surface. People with this mutation are otherwise normal. (Incidentally, this mutation is present pretty much only in Europeans, not in Africans or Asians.)
Finally, the most common strains of HIV require CCR5 (rather than CXCR4) as a co-receptor.
Hypothesis
If a chemical can be found that blocks human CCR5 receptors, and it can be made into a drug, it should be effective against HIV infection.
Hypothesis testing
Using modern biochemical techniques, a CCR5 inhibitor, known as Maraviroc, was discovered. When tested against the virus in vitro, it blocked viral entry into cells. Further, it didn't interfere with other HIV medications. Because this worked in the lab, pilot studies were down on small numbers of patients, and these patients had significant drops in the numbers if virus particles in their blood, without serious side-effects.
But wait...
DrPal, didn't you say that there were strains of HIV that use the CXCR4 receptor (X4 strain) rather than the CCR5 receptor (R5 strain)? Yeah, I said that. This fact has a couple of consequences. First, before using this new drug, patients are tested to see if their virus is X4 or R5. Second, we might predict the following: if a mixed population of R5 and X4 strains is exposed to a drug that inhibits replication of R5 viruses, selection pressures should favor X4 strains. According to the cited studies, this does appear to happen, although the clinical significance of this fact is not yet clear.
I'm thinking about winding this up soon, but first...
Maraviroc represents an entirely new class of HIV medications. It's discovery is a nice example of the way science-based medicine works: an idea consistent with observable reality is posited, tested, and implemented. Implausible medical claims, such as homeopathy, acupuncture, and chiropractic, start off with ideas that contradict what science tells us about how reality works. If that weren't enough, they then are used despite overwhelming evidence against their efficacy. And if that weren't enough, when the apologists for these practices run out of anecdotes to support their use, they fall back on the deus ex machina of conspiracy theories and "other ways of knowing". When it comes to medicine, there are no other ways of knowing. Abhorring science in favor of various forms of mysticism will do nothing more than waste your time and money. Science may be hard, but it's awfully fun, and it's still the best way we have of understanding and manipulating reality.
References
Roy M. Gulick, M.D., Jacob Lalezari, M.D., James Goodrich, M.D., Ph.D., Nathan Clumeck, M.D., Ph.D.,, Edwin DeJesus, M.D., Andrzej Horban, M.D., Ph.D., Jeffrey Nadler, M.D., Bonaventura Clotet, M.D., Ph.D.,, Anders Karlsson, Ph.D., Michael Wohlfeiler, M.D., John B. Montana, M.D., Mary McHale, M.B., B.S., M.R.C., John Sullivan, B.Sc., Caroline Ridgway, M.Sc., Steve Felstead, M.B., Ch.B., Michael W. Dunne, M.D.,, Elna van der Ryst, M.B., Ch.B., Ph.D., and Howard Mayer, M.D., for the MOTIVATE Study Teams* (2008). Maraviroc for Previously Treated Patients with R5 HIV-1 Infection New England Journal of Medicine, 359 (14), 1429-1441
Gerd Fätkenheuer, M.D., Mark Nelson, F.R.C.P., Adriano Lazzarin, M.D., Irina Konourina, M.D., Andy I.M. Hoepelman, M.D., Ph.D., Harry Lampiris, M.D., Bernard Hirschel, M.D., Pablo Tebas, M.D., François Raffi, M.D., Ph.D., Benoit Trottier, M.D., Nicholao (2008). Subgroup Analyses of Maraviroc in Previously Treated R5 HIV-1 Infection New England Journal of Medicine, 359 (14), 1442-1455
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And it's only because we don't think that it occurs naturally that we couldn't do the same for the CXCR4 strain?
I'm usually *for* medications that eliminate large parts/majorities of diseases, but this one sounds as though it might help an outbreak of the cxcr4 brand of strain.
I just woke up so i'll explain better if i have to, but think of it from an evolutionary standpoint: Less CCR5 infections + knowledge that there's a drug combating infections + the lack of a natural defense (IE what the europeans have) + [...] = MORE CXCR4 infections, which we can't do anything about.
This isn't really like the HPV vaccinations we have, which is what i figure the most likely non-medical person would give me as an example.
The thing that worries me about viruses is how hard it is to completely eradicate them from our lives compared to other nasty wiggly body things we can get infected with, I just don't want to see a super-drug-resistant HIV strain going around. Speaking of which, have there been any studies into how HIV has progressed in the last 30 years (mutations, etc)? If so could you link some, pretty please?
http://www.nature.com/nrd/journal/v6/n12/full/nrd2336.html
All the things you've mentioned are well-known to HIV docs. I'll explain more in another post.
How about some real electron micrographs to go along with the very nice cartoon Dr. Pal, or are you trying to give us another snow job?
Oh! Another troll for the Trollympics?
Hm... alleging fraud with no evidence, check. Calling well-rendered scientific illustrations a "cartoon", check. Linking to an *extremely* denialist website, check.
Could be a contender! Stay tuned for more exciting details! (and mockery!)
This is supposed to be an informative discussion, denialists aren't welcome.
I went poking around that rethinking aids site for about 5 minutes and couldn't find what exactly they are proposing to replace the HIV/AIDS hypothesis. What is causing AIDS Mr Carter?
Once again, as in all of my science-y posts, please forgive any oversimplification.
No, I would much prefer to thank you for it. It's nice to be able to understand wtf you're talking about and I don't know a lot of the relevant terminology. A non-simplistic version would be absolutely pointless to someone like me and I like to think that folks like me are your target audience (you know, people who don't have relevant degrees, but are interested)
I find this really interesting because I am reading Virtual Light by William Gibson right now. In the future described in the novel, there has been a HIV vaccine that was developed from a male prostitute who was found to be HIV positive but not only didn't get sick, but made some of the HIV positive men he serviced get well. Turns out that the strain he was infected with doesn't harm it's host and will kill off other strains of HIV. So in this future, everyone is purposely infected with this strain of HIV.