Moderna’s HIV Vaccine Prepped for Trials in Africa | Hacker News Reader

Moderna’s HIV Vaccine Prepped for Trials in Africa

pharmaphorum.com

202 pointsTrouble_00798 comments

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.

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.

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.

> 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.

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

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...

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?

Some numbers for people interested in HIV:

Many countries in southern Africa have adult prevalence rates of >10% of HIV. In other parts of Africa most countries have a prevalence of ~1% or less. On other continents most countries have less than 1%, including the US with 0.3% adult prevalence. [1] For all the people wondering why this vaccine is being tested where it is, it's because just like we did for the covid vaccine, you split people up into placebo vs vaccine groups and then wait to see how many people get the virus from each group. If rates of HIV infection are as low as in the United States, you'd need to test the vaccine on ~100-1000x more people to see if it worked.

Non sequitur, but too interesting not to share: The estimated risk of acquiring HIV from a single sexual act is way lower than I realized until recently. Receptive vaginal sex with an infected individual is estimated to lead to infection only 8/10,000 times. Receptive anal sex is ~10-20 fold higher, 138/10,000. Sharing needles with an infected person is 63/10,000 [2]. That means you could have an ejaculates worth of HIV virions in your rectum, and be uninfected 49 times out of 50. (However, HIV infects immune cells, so it's way more likely to find an immune cell to infect if there are more in the area. That means infections or inflammation from other causes increase your risk of acquiring HIV compared to having no infection or inflammation. Similarly, way more target cells in blood, so if you have epithelial damage your risk goes up.)

[1] https://en.wikipedia.org/wiki/List_of_countries_by_HIV/AIDS_...

[2] https://www.cdc.gov/hiv/risk/estimates/riskbehaviors.html

Yeah and for men doing vaginal sex the risk is way lower of getting infection than being the receptacle.

HIV had to be rebranded away from being seen as a same-sex curse to a common ubiquitous threat in the 1990s to get society to care, but its really not something thats as big of a threat for most of us as it was suggested. A lot of it was just not accurate. Generations of heterosexual people running around scared. Probably did slow transmission down, since only “heterosexual” and bisexual men were/are spreading it to women via sex. But also viral load is suppressed and suppressible now.

I mean, for women in southern Africa, some communities have HIV prevalence of ~40% to this day. 4 in 10. Despite the lower risk associated with individual instances of vaginal sex, it absolutely is something to be worried about in those communities. And because those communities have lower access to healthcare, it often goes undiagnosed and untreated for far too long.

Yes, the reality in some countries on that continent is very different, there is no parallel to the west

Another caveat is that infectiousness is correlated to the current viral load of the HIV+ partner in all of these acts. Most estimates like the ones you give are averages for all viral loads at varying stages of HIV infection.

Someone about a year into the infection will be around the natural low-level during the dormant phase, with perhaps only 10,000s of viral copies per ml of blood. Someone a few weeks after infection, or in the early stages of AIDS after some years, can have millions of copies per ml. The relationship between viral load and infectiousness seems to be, approximately, a simple exponential curve. One Australian study found that your odds of infection with receptive anal sex with a newly HIV+ partner at peak viral load could be as high as 1 in 3, while in the latent phase in may be more like 1 in several hundred, or even lower.

I hope this is successful. I really do. Given the long dormancy of HIV I really wonder how success is going to be effectively measured. Won't it take years?

The mechanics of how a single cell works is mind-blowing. The mechanics of how HIV works is even more mind-blowing. The replicatin process, how it infiltrates a cell, how it avoid detection and how it defeats the body's defenses.

This sort of thing gives me a lot of confidence that pretty much any new virus we see is natural because nature is a whole lot better at making viruses than I think any lab could be. The best a lab could really do, at least at this stage, is gain of function on an existing virus.

Nature is good at what it does because it has time on its side. We humanity don't need ever everlasting immunity- we just need something that work for 20 years, then we will have something newer and better.

Modena and BioNtech will be the future Microsoft and Apple in the corporate landscape.

They are headed for great things.

I will never read "Africa" and not roll my eyes. The trials are set to take place in literally just two countries! Every single use of the word seems to perpetuate the stereotype that the entire continent is ravished by famine and disease.

Well I think this is really your own bias. The article quickly states that it is being rolled out in 2 African countries.

It also fits the context. Countries with the most cases are Russia and almost all countries in Africa (except for the North). So Africa as a continent is in need of a HIV cure.

I'd love to know how "Moderna's HIV Vaccine Prepped for Trials in Rwanda and South Africa" doesn't fit the context.

It would also fit the context, but 'Africa' does also.

If this were rolled out to a couple of states, would "in the US" be wrong too?

Africa is not a country.

It also contains some of the most diverse individual countries in the world, like Nigeria.

I never claimed it was? That's a non sequitur.

It's literally the crux of the issue.

If it was rolled out it France and Sweden, the title most likely wouldn’t say “in Europe”.

It depends. If almost every country in Europe had high levels of infection why wouldn't they use Europe?

I read the title about Africa as a positive announcement for the whole continent.

I think you would have a hard time in Africa; Africans themselves tend to have a stronger affiliation to their continent than country and refer to it as-such.

I was born and raised in Africa and I disagree.

This comment reminds me of this part of a speech[0] from a nigerian writer:

I must say that before I went to the U.S., I didn't consciously identify as African. But in the U.S., whenever Africa came up, people turned to me. Never mind that I knew nothing about places like Namibia. But I did come to embrace this new identity, and in many ways I think of myself now as African. Although I still get quite irritable when Africa is referred to as a country, the most recent example being my otherwise wonderful flight from Lagos two days ago, in which there was an announcement on the Virgin flight about the charity work in "India, Africa and other countries."

[0] https://www.ted.com/talks/chimamanda_ngozi_adichie_the_dange...

There are over a billion people on the continent with several countries and hundreds upon hundreds of languages.

You're gonna have a hard time assuming things about Africans as a group regardless of your stance

> Africans themselves tend to have a stronger affiliation to their continent than country

My impression is exactly the opposite. We don't even like our countries that much, LOL. Tribal affiliations run strong. Sorry.

EDIT: I've always felt that the "African" identity is pushed by non-Africans looking from an outsider's perspective, and our own social/political elite trying to reshape the post-colonial continent.

I remember an interesting HIV campaign that went something like

UVL=0VL

It made me think.

(undetectable viral load = zero viral load)

Perhaps this vaccine will not cure HIV once and for all just yet, but maybe it can work as an alternative to PrEP by keeping the viral load down?

I think you're thinking of "U=U", which stands for "undetectable = untransmittable". At this point in the epidemic, most transmission happens from people who don't know their status, and not from people who are known to be HIV+ and are in treatment.

I presume that this is an official trial. Because i saw a documentary 10 years ago about Pharma companies testing (also HIV) vaccines in Africa.

Several HIV vaccines have been tested. None have been successful yet.

This is an official trial, but it's just Phase I, to see if it's safe. A few vaccines have made it to phase III, but nothing passed yet.

I doubt it will fare much better than J&J HIV vaccine with 25% "efficacy".

https://www.nytimes.com/2021/08/31/health/hiv-vaccine-south-...

You know we truly live in an insane world when Immunostimulants are not attempted for HIV despite being the obvious treatment.. The mediocrity goes beyond imagination. Thymalin +- thymosin a1 +- thymosin b4 are extremely likely to be the best available cures, Thymalin increase naive T cell production by 680% and the thymosin strongly stimulate T helpers and the adaptativity of the immune system. The major component of HIV is an abrupt thymic involution but hey let's not give them the thymic hormone h o h o https://pubmed.ncbi.nlm.nih.gov/15078181/

lol thymalin defficiency is even found to be the cause preceding AIDS so let's not use it h o h o

> Abnormally low plasma thymulin levels preceded the development of peripheral blood T cell abnormalities. https://pubmed.ncbi.nlm.nih.gov/3018210/

I'm afraid no one cares for those people.

https://pubmed.ncbi.nlm.nih.gov/16940531/

Who knew I'd click on HN and come across the cure for HIV!

who knew people being in denial of actual potent research would maintain the ignorance of those treatments? https://pubmed.ncbi.nlm.nih.gov/33237528/

I recently replied to a comment of yours where you went on a tirade against benzodiazepines saying there are safer compounds that mainstream medicine chooses to ignore, and here you are doing the same thing with HIV treatments.

Anyone cares to chime in and explain why it is not so simple like OP implies it is? Again, I very much doubt mainstream science is completely ignoring the panacea and preferring suboptimal solutions. Smells too much like a conspiracy theory to me.

> I very much doubt mainstream science is completely ignoring the panacea and preferring suboptimal solutions.

"Mainstream" medical science is driven by a massive conflict of interest due to relying on funding from pharmaceutical companies and bureaucrats with a financial interest in pharmaceutical companies. This is why for decades mainstream medical science insisted smoking was healthy. There's a great book on this: https://www.amazon.com/Real-Anthony-Fauci-Democracy-Children...

Well, in Russia treatments to boost your immune system are a thing and they're used by people with herpes or hiv - before talking to Russians I had no idea they even existed. Some people report good results, others no change. It's not a final solution but it's not that expensive and it could be something western people would choose as well if it was an option. I can't say whether it's valuable or placebo effect but there is not much literature on the subject.

Some researchers in India came up with RISUG, a permanent but safely reversible male contraception. It's literally a piece of plastic, no hormones giving you cancer like female contraceptive, no life subscription to buy condoms and without the risks of a vasectomy. The treatment is so cheap that it never had financial backing and we're still stuck with subpart alternatives.

After being prescribed benzodiazepines I ignored the prescription because of how addictive they are and self medicated with cannabis. That's a substance which can be an alternative (in some cases), it's not addictive and doesn't give you withdrawal symptoms. And yet, it's still mostly illegal and getting a prescription is insanely hard, even when you qualify. Because of a condition I have, I qualify for medical cannabis in the country where I reside and I still haven't been able to get a valid prescription in 3+ years.

Cannabis can very well lead to dependency, I struggled with it for the majority of my adult life. I totally agree that illegalising it is laughable and it's by no means as dangerous or easy to get addicted to it as is the case with benzodiazepines, but it is also no joke. Of course I am talking about "recreational" use, not medical.

I really dislike the handwaving nature with which the very real and especially psychologically quite harmful side-effects of Cannabis are discussed for the most part. Mind you, I believed it to be harmless for the longest time, too.

> Cannabis can very well lead to dependency

My eyes near roll through my head when I hear people say this.

Anything can lead to dependency. ANYTHING. Sex, judo, farting for attention. Scratching your sack. Making shitty tik-toks.

The withdrawal symptoms for cannabis are so, so, so so far from that of opiates or nicotine; or benzos, as you mention, that yeah, you can basically say there are no withdrawal symptoms.

Some people are prone to dependence on things, due to their physiology or psychological make-up. Those people are far, far, far better off using cannabis than benzos or opiates. Look at how much deaths from overdoses go down in legalized areas. That applies in both medicinal and recreational contexts.

> ...very real and especially psychologically quite harmful side-effects of Cannabis

Wut. Quite harmful compared to what - water? Water kills more people than cannabis does.

On balance, far more people find psychological benefit than harm from cannabis. Same with physical health. Handwave that away.

Compare the side-effects from cannabis to ibuprofen. Come on man, let's keep some perspective here.

> Anything can lead to dependency. ANYTHING.

So, who cares, right? Withdrawal symptoms of sugar are nothing compared to opiates, yet it's a bigger epidemic than opiate addiction. But since it doesn't make your skin crawl and hallucinate, it doesn't matter?

Cannabis is quite benign in the grand scheme of things, but let's stop saying it's the cure to all problems and that it has no downsides. Like GP I have been through the marijuana addiction phase and it wasn't fun. I'm prone to get addicted to stuff, so that's on me, my quitting my 5 joints a day was almost as hard as quitting my pack a day smoking habit. The difference is that smoking didn't turn me into an idiot pot-head that burned away a big part of his teenage years, of which I can't remember much. Certainly nicotine didn't trigger my anxiety which almost turned into psychosis like THC did. Talking just about dependency and the physical withdrawal means ignoring a big part of what marijuana smoking actually does, something stoners really do not want to talk about.

> So, who cares, right?

Right. I don't like sugar being in everything, but I don't cry about evil sugar making me buy pop rocks and ice cream. I don't want sugar to be banned, or to force rehab on people guzzling too much cola. Ending the crazy ass subsidies for corn syrup would be nice though...

> let's stop saying it's the cure to all problems and that it has no downsides.

For every time I've heard someone say that cannabis is a pancea, I've heard 100 people say people need to stop calling it a panacea. It's so tiresome.

> turn me into an idiot pot-head that burned away a big part of his teenage years

Pfft, you did that, not cannabis. Cannabis didn't hold a gun to your head and say smoke me, like heroin or nicotine. Yeah, under 18yos shouldn't smoke. That point gets lost in all the nonsense left over from decades of misinformation. Making it illegal makes that issue far worse, through increased availability to teenagers, and awful contaminants.

And yeah, THC has a (poorly understood and far from straightforward) link with psychosis. So if you're feeling that, then get a high CBD strain, or don't smoke. That's common knowledge and not something to twist your pants over.

Pharmaceutical companies always chose Africans for medical experiments

While your point is well taken given historical context of rampant risky medical trials conducted against african and african american populations that are pretty horrifying, I suspect it has more to do with the high concentration of HIV per capita in Africa. To my knowledge, Africa had one of the highest HIV rates in the world so I suspect this is still the case making it a very reasonable region for the trials.

If you had an "obesity" vaccine, the US would be a good population to do trials vs say Ethiopia or Sri Lanka. If you have a Dengue vaccine, you probably wouldn't want trials in northern Canada but would probably target southeast Asia instead.

this isn't an experiment, it's a trial. Companies don't always do trials in Africa; in fact, they expanded into Eastern Europe and Asia moreso. HIstorically, Africa wasnt used for running trials, nor was it a place were lots of 'experiments' were done. Please get facts correct.

Back to testing vaccines in poor helpless countries.

I'm sure a lot more of these trials will be pushed now that safety monitoring/controls and study quality requirements were relaxed so eagerly for the covid vaccines (and I mean well past the point of the initial unknowns that require leeway).

These companies can see dollars as far as they can imagine and public perception has swung incredibly from the lowest of trust groups to the higher brackets.

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