> It is not entirely understood why some patients are able to achieve undetectable viral loads without ART.
In no way saying this is not a good thing, but do we know if this can be sustained for the whole lifetime?
Or is it that 20, 30 years later, as people get older the person eventually gets AIDS?
> if the person with HIV started ART with a CD4 count above 500, they would be expected to live to the age of 87 – a little longer than those without HIV.
https://www.aidsmap.com/news/mar-2020/yes-same-life-expectan...
it's really interesting to me that their health becomes poorer earlier, but that it doesn't affect mortality.
And as it's 'just' prevention, it's hard to know whether it will reliably improve this individual outcome...
Merely exposing someone to a virus does not necessarily result in widespread infection. A low enough number of copies could be neutralized by the host's immune response before it has a chance to spread significantly. How low this number is depends on the virus. For example, COVID-19 load is higher in symptomatic patients.
Chronic viral infections are managed by reducing as much as possible the number of viral copies in circulation. Risk of transmission is mitigated when number of copies is low enough. There are studies showing risk of HIV transmission approaches zero when HIV load < 200 copies/ml. Ideal would be HIV load < 50 copies/ml or undetectable.
https://en.wikipedia.org/wiki/Viral_load
https://en.wikipedia.org/wiki/Minimal_infective_dose
https://www.virology.ws/2011/01/21/are-all-virus-particles-i...
https://royalsocietypublishing.org/doi/10.1098/rspb.2009.006...
https://www.cdc.gov/hiv/basics/livingwithhiv/protecting-othe... https://www.nejm.org/doi/full/10.1056/NEJMoa1600693#t=articl... https://pubmed.ncbi.nlm.nih.gov/27404185/
You don’t need to be a 100% sure. Once the risk becomes small enough you can spend your time worrying about other risks.
Hell, an HIV viron could be created spontaneously through quantum tunneling in your body with some non-zero probability. I think it would be legitimate to triple equal signs that to "not going to happen" though.
Time spent driving is not time spent having sex (well, hopefully).
So if risk(dying while driving) ~ risk(dying because of sex) ~ 0, you can easily ignore both of those.
Also, you can avoid having sex with a HIV-positive person. You can probably not avoid driving. So the fact that a risk may be low is not sufficient to take such risk if you can hedge against it.
Meanwhile doing some once a day with a 1 in 1,000,000,000 chance of possibility killing you in 40 years just isn’t worth considering.
Depends what your quality lifespan is. If I get sick of everything, that time isn't worth much.
There's also a "time-value" of life.
Cool stuff I can do today may be worth a lot more to me than things I can do 500B years from now. Especially since the person that would be doing them is someone I cannot identify with at all.
Yes, and I believe this is a reason why people make choices that adversely affect their 50 year old self. Who's that guy in the future going to be? Why should I care about making it better for him?
I can imagine time scales on a par with how long I've lived and to a lesser extent to the ages of people I identify with.
(500 year from now me would see the first paragraph as exceptionally foolish... and also inevitable. But that fact doesn't change the truth of what I'm saying).
The vast majority of virions seems to be killed by the immune system before they can actually take hold.
https://journals.plos.org/plospathogens/article?id=10.1371/j...
Some Sex lubes can make it easier for infections to get into the body. https://en.wikipedia.org/wiki/Personal_lubricant#Water-based
Thing is I wonder if a higher vitamin A and zinc intake can help because all epithelial cells need retinol (vitamin A), zinc is needed to move retinol around the body as Retinol Binding Protein (RBP) for epithelial cells. Alcohol can reduce fat soluble vitamins stored in the liver which can then reduce the VitA stored in the liver, you see this most easily with alcoholics and hypovitaminosis A, but even short term binge drinking can reduce levels enough to increase risks of transmission which probably explains man flu!
I found a cadaver study where they measured vitA content in the livers of dead people but didnt say how they died, knowing that you can die from ingesting too much vitA in one go like some arctic explorers did when eating polar bear livers decades ago and died. In order to get the highest amounts of vitA seen in some of these cadavers, you'd have to consume 30,000ui of VitA every day for at least a year without your body using any! Thats a lot of Vit A!!!
Anyone who paid attention to the Ebola outbreak in Africa a few years back, may remember that some viruses like Ebola can hide in parts of the body where the immune system can not go, namely the eyes and the testes and sometimes the brain, so they may have remembered that blokes testing negative for Ebola but previously had it, could still be passing it on through semen.
The thing with HIV, its typically passed through anal intercourse, not vaginal where there is sufficient lubrication, but its passed more frequently in Africa because they have a tendancy to have dry vaginal intercourse, because they actually try to reduce the wetness of the vagina which then creates microtears and sores and then its easy for HIV to get into the bloodstream, just like cuts and sores in the mouth also making it easy for HIV to get into the blood.
The whole 80's govt advice/warnings on HIV were directed at everyone because they didnt want to stigmatise those engaging in non vaginal intercourse.
The biggest risk from HIV is getting it into the blood, like most things which are pathogenic.
Now you can still have a highly effective immune system which can lock down viruses, but there is always the risk it gets into those parts of a body where the immune system cant go and I dont know what they test now a days.
Gay people were so stigmatized at the time that the government did nothing when they thought it was a 'gay disease'; they just let an epidemic spread and people die. Very few in the 1980s worried about offending gay people. Once it was spreading to people who weren't gay, then I'm sure health information was provided to those people.
But I just have to laugh out loud at the thought of governments in the 80s not stigmatizing the disease and specifically queer people having anal sex.
Just so laughably the opposite of the real experience of an entire lost generation of gay men.
There's no excuse for it in todays day and age, but what can you do? I sometimes think democracy is a soap opera for serious people, whilst the military run the real show.
There was a thing not long ago where talcum powder, I think Johnson & Johnson, had some asbestos contamination (asbestos being another mineral that can come from the same mines, apparently). And people were suing because it gave them cancer of the uterus and other internal parts of the female reproductive system. Which makes you go: Wait a second. How the hell does that happen?
That's how.
When I first heard about asbestos in children talc powder, I simply thought it was just one of these "bad pharma" conspiracy theories (there was another one - about asbestos in sanitary towels). It seemed so far-fetched - who in their right mind wouldn't make sure to thoroughly check a product designed to have long-term contact with babies' skin against well-known carcinogenic substance? Well, it turns out this time it happened not in China but right in the heart of the USA.
You might find this interesting, the "few years back" might be now again: https://www.nature.com/articles/s41586-021-03901-9
I think this Hollywood film Dont Look Up will be a poignant message to everyone.
I would not use Wikipedia for health information with serious consequences.
I mean, technically, there's always a possibility of getting HIV. Particles in your body could spontaneously quantum tunnel at the same time into the form of an HIV virus. This is basically impossible, but not actually (p = 0.00) impossible.
At some point you have to look at a probability and say - that's basically not transmissible.
You generally can't measure infectious dose directly without a highly unethical challenge study. You can sometimes know concentrations that did or didn't result in infection in various real world scenarios, and sometimes you have circumstantial evidence (e.g. you can know how much virus a person sheds, and what proportion of a room with certain ventilation quantities got infected).
Infection requires virus particles to be physically present in transmission vectors (fluids, droplets, etc). There's generally also a dose-response effect where more particles means more chance of evading the immune system well enough to establish replication in the victim.
So a lack of anything to detect, means a lack of anything to spread an infection.
One should add that for that the threshold for detection has to be lower than the threshold for infection.
Example: let the detection threshold be 10 particles/ml and the infection threshold be 100 particles/ml (*) -> then undetectable implies that it is very improbable that an infection will take place.
(*) This is a very crude description. Think of it like this: Every single virion (virus particle) has a very low probability of causing an infection itself but there is a high number of them and for one them it might just work out (higher viral load -> higher risk of successful infection)
This statement is logical and makes perfect sense - but it's narrower than the original one.
We're quite good at detecting viruses if we really want to. PCR can amplify DNA so much that we can detect even 50 viruses per milliliter of blood. A milliliter seems like actually a lot of blood to get into someone else and your innate immune system is capable of finding and neutralizing small amounts of contagions relatively well even if it's never seen it before. I do suspect this is a statistical impossibility though probably you could somehow get incredibly unlucky, for example in your blood momentarily all the free floating viruses end up in the same bit of blood and that somehow gets into someone else, but I think we can all realize that probability is tiny and in practice I don't think there are any examples of transmission with undetectable levels of HIV.
1 cm^3 is indeed pretty big. That’s 1,000 little millimetre cubes, and we can detect as few as 50 virions in that space!
I will point out though that 1 ml is low for semen (more like 2.5 ml or more).
Think of it like chemistry. Sure, two covalently bonded hydrogen atoms at STP could have nuclei 1cm from each other due to random chance. However, the probability of this happening is so low that it is effectively 0.
If one bounds the risk from HIV from an undetectable partner to an unmeasurably small epsilon, dwarfed by other risks by many orders of magnitude--- the edges where the assertion are false don't matter.
Anybody remember hearing something like this?
In many cases. One case, for example was identified from a prostitute in sub-saharan africa who managed to be completely HIV-free. It turned out she had a mutation in her antibodies that caused the antibodies to latch onto things with four sites instead of just 2 (think X shaped instead of V shaped).
https://www.iavi.org/news-resources/press-releases/2022/iavi...
Sounds like the mRNA platform is being tested as a delivery mechanism for immunological work that was done separately.
mRNA eliminates all of that. The 2 immune pathways can be combined into 1 vaccine, and the multiple vaccines can all be produced with the same synthetic pipeline and the same distribution and administration requirements.
mRNA may make a huge difference here.
I am not sure about the XNAs. You might be able to get around it with increasing the dose (trivial if you are producing your own RNA) or it might be possible to use XNAs in a standard synthesis protocol. It would depend on the RNA Pol I think.
Traditional way to do this is recombinant approaches (mentioned). These are also in progress. mRNA is much quicker to iterate, though. They tried a few candidate sequences in sHIV to guide their human vaccine development.
mRNA vaccines are kind of neat in the way that they create a few day long pulse of new virus-like particles showing up, to ensure the immune system gets really annoyed.
Ref: https://en.wikipedia.org/wiki/Simian_immunodeficiency_virus
However, the mRNA vaccine may be more stable in a way that makes it easier to make or store or for entrance into the body. Not to mention purification steps may be easier. You don't need to make this in some exotic cell line which creates a protein soup you have to purify. It may be easier on the body (less likely to develop a severe immune reaction), or it may be better at generating a sufficient immune reaction because a lot of mRNA development has gone into finding molecules that are readily taken up by the immune system regardless of cargo.
These are a few reasons I can think I am sure I am missing some and there may be a stated answer out there that I have yet to search for.
Actually, a whole lot of recombinant approaches have moved to human trials (along with viral vector approaches). They early ones showed no efficacy; the newer ones we just don't know (yet).
The main benefit of mRNA is iteration: you can try a whole lot of different protein mixes and see what works best in an animal model. A secondary benefit is that the sustained churning out of proteins for a few days seems to generate a much broader antibody response, making getting some of those elusive bnAbs more likely.
A big problem with killed HIV vaccines and purified fragments of HIV is that growing virus in human immune cells is extraordinarily costly, and you really wouldn't want to have some live HIV leak through your purification process. So this is why we're mostly talking about other approaches to make proteins (viral vectors, recombinant DNA in bacteria and other cells, mRNA vaccines, etc)
I should have been more clear here, I meant specifically trials of what I presume could have been attempted if the vaccine was expressed as protein instead of mRNA. But thanks for the clarification. And the mention of viral vectors which are an area I was less aware of till recently but it has been cool to see them in more places.
Yes, and one vaccine approach is getting a bacterium or other virus to make a lot of a protein you're interested in, and then purifying the stuff you're interested in and forming it into a vaccine product. These are recombinant approaches. E.g. https://en.wikipedia.org/wiki/AIDSVAX is exactly what you describe: a viral protein vaccine developed using recombinant approaches from e.g. Chinese hamster ovary cells https://pubmed.ncbi.nlm.nih.gov/8142140/
The first was a hepatitis B vaccine developed in the 1970s where yeast cells were modified to make hepatitis B proteins. Then the HPV vaccine used the same approach, choosing proteins that would spontaneously assemble into a virus-like particle that triggers a strong immune response.
Complicated proteins have to come from a living thing, in practice. So if you're going to administer a viral protein, it has to come from purifying virus that you've grown or from a recombinant approach of some kind (and growing HIV is problematic for multiple reasons).
mRNA vaccines are particularly useful because you can substitute bases with N1-methylpseudouridine which makes them identify as "self" by TLRs and doesn't generate counter-productive innate immune responses. You do need an adjuvant so that the cell produces more MHC displaying the antigen and attracts lymphocytes but the nanoparticle works to do that.
The result is a very small message payload to the immune system that targets the correct system. Viral vectors all have more "stuff" all over them which are going to trip other parts of the immune system (or cause side effects like the PF6 interaction with the Adenovirus capsid that is responsible for the rare clotting effects).
Previous HIV vaccine attempts have only done a fair job at eliciting these broadly neutralizing responses. e.g. SAV001, a "whole killed" HIV vaccine, only produces broadly neutralizing antibodies in about a third of recipients (and less broadly neutralizing response in a much bigger fraction).
The mRNA approach, like some recombinant approaches, seeks to generate just portions of envelope protein to tailor the response to produce these bnAbs.