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Comment by bigDinosaur | Hacker News Reader

One thing I didn't realise with HIV is that initially the body does produce effective neutralising antibodies. That's what causes viral levels to decrease for the first few months, and also the slow decline that characterises chronic HIV before it turns into AIDS. It's just that HIV mutates far too quickly and the body cannot keep up. This makes me less hopeful about vaccines. I assume one will succeed eventually, just that it's a slog and will have many more failures.

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> It's just that HIV mutates far too quickly and the body cannot keep up.

* Most bodies cannot keep up. But some bodies can[0]. And that fact is why I remain optimistic that even if this isn't the vaccine that cures HIV, that we will one day find one.

[0] https://en.wikipedia.org/wiki/Long-term_nonprogressor

I recall reading somewhere that in apes, some species have lots of endemic SIV and don't get symptoms, but other species will die from it.

Broadly-neutralizing antibodies[1] which target non-variable sections of the virus are known - it does have a few conserved regions and the focus has generally been on hitting it there. The thing is, there are people who produce these types of antibodies and we know what they look like - but the trick is how to generate them successfully.

There's a whole fascinating set of interacting factors which HIV sits in a unique intersection of, but we are capable of building successful antibodies against it - it just takes years, which naturally we normally don't have (probably also some unique genetic factors).

[1] https://en.wikipedia.org/wiki/Broadly_neutralizing_HIV-1_ant...

It's not even just that HIV mutates quickly. After the initial attack, it infiltrates the immune memory cells and injects itself into your DNA and lies dormant for a long time, while these immune cells reproduce happily.

My understanding (of course it could easily be wrong, always verify this stuff) is that it's actively suppressed in the 'dormancy' stage, and it's more an almost inevitable failure of suppression that allows it to stop being 'dormant' so to speak.

Yes. It can take up to a decade for AIDS to develop after infection. The number of viral particles in the blood will peak shortly after infection, and it can cause flu-like symptoms for a week or so. And then the immune system will ramp up and it's almost fully suppressed. But some T4 cells have been hijacked and are spitting out HIV which is hijacking other T4 cells. This requires destroying the infected T4 cells. And a war of attrition and cumulative damage of a long inflammatory response eventually leads to increasing failure in that suppression. (Same caveats apply to my understanding.)

> This requires destroying the infected T4 cells Which is the trivial role of newly produced naive T cells and therefore thymalin cf my comment

I feel like the real fix for HIV is crispr editing of bone marrow to eliminate the receptors the virus uses to enter lymphocytes and B-cells.

I will not be first in line for that treatment

> I will not be first in line for that treatment

That would apply to any treatment. Many the most successful treatments we have now killed and maimed initially.

How does the body keep up initially? If the body got from viral load N to N/2 despite HIV mutating, then why can't it go from N/2 to N/4? Does the body slow down or the virus speed up?

My assumption -- with the initial infection the body creates antibodies to fight off that original strain. As it spreads to more and more cells and churns out copies, it mutates slightly every time it replicates. And then each of those instances replicates and mutates a little more, becoming a bunch of different strains. And while initially the original antibodies will be effective to start with those strains, eventually they'll muttate enough to where you have so many different strains where suddenly the antibodies aren't working anymore and that's probably the point where the immune systems gets overloaded trying to produce antibodies for all these different strains, and as soon as it catches up it all becomes worthless, because in the meantime a ton of other different strains have mutated in the meantime, and so on and so on.

tl;dr snowball effect

Perhaps the strain that spreads well is easy for antibodies to kill; but mutates easily into a variant that doesn't spread very well, but is very hard to kill.

Not an expert here, but my layman's understanding is that as it is a disease that attacks the immune system the bodies ability to fight off each new generation is gradually diminished until eventually it is not able to fight off the new mutations any more.

If they are going thru trails then they have probably found a way to attack a mutating virus that others had not. I wonder if they are targeting multiple areas on the virus at one time. One of the advantages of mRNA vaccines is that they can be very precise as to where they attack the virus by getting the body to create the needed antibodies and the vaccine can be created very quickly. Moderna talked about creating the covid-19 vaccine in days once they got the virus' DNA sequence. That seems like an advantage for combating the HIV virus. Can you imagine being able to create a custom vaccine per individuals after the virus mutates? Sounds like science fiction but it seems like a possibility given the technology.

Does anyone have any idea what their new approach is?

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