HIV is notoriously unstable - RNA viruses don't contain any error checking during replication. Which is one reason HIV drugs, including those one, are almost always used in combination.

coronaviruses are also RNA viruses, fwiw

It’s a different kind. HIV is a retrovirus in that RNA is reverse transcribed into DNA. Coronavirus transcribes to RNA directly.

There are several variant-resistant pan-Covid/pan-Sarbecovirus/etc. vaccines under development [1], including one by the US Army [2].

Vaccines are notoriously slow to develop, perfect, and test for safety and efficacy. The original Covid mRNA vaccines were developed at breakneck speeds as far as vaccines go. Unfortunately, much of the funding has since dried up.

In fact, it's HIV that's much harder to develop a vaccine for. HIV vaccine research has been going on for 40 years and hasn't really had any candidates that went beyond "plausible" until recently.

[1] https://www.nature.com/articles/s41423-023-01116-8

[2] https://mrdc.health.mil/index.cfm/media/news_releases/2021/p...

The covid vaccine was barely a vaccine. It was more like a flu shot in its efficacy and with significant more side effects

Uh, no. It's actually extremely effective against the target variant. The original Wuhan strain is extinct as a result. In areas with high vaccine uptake, the population has very high levels of neutralizing antibodies against it, to this day. Even if it somehow broke out again, it would die off within weeks, as most of the population is immune to it.

Evolution has driven the virus away from the neutralizing antibodies. This is called immune escape. Recent variants have very little antigenic overlap with the original strain. The original antibodies are not very effective, so people can actually get sick once again.

The FDA now updates the vaccine formulation every year. This means that every year, there is a time window during which the vaccine formulation and the circulating variant are the same. If you get an updated shot as soon as it becomes available, you're immune for all practical purposes until a new variant emerges.

Right, but most diseases we have vaccines for can’t easily evolve their way out of them like in this case. That’s kind of the point.

And you’re far from immune with the newest formulations. From the CDC: “People who received the updated COVID-19 vaccine were 54% less likely to get COVID-19 during the four-month period from mid-September 2023 to January 2024.”

https://www.cdc.gov/ncird/whats-new/covid-19-vaccine-effecti...

Even with the original strain/vaccine, effectiveness waned after 6 months.

The updated 2023 vaccine was based on XBB.1.5. In the period you quoted, the variants based on the massive BA.2.86 saltation took over, including JN.1 which was fully dominant by January. XBB.1.5 and BA.2.86 are antigenically very different. I would not be surprised if the case ratio between the two branches during the period was in fact 55:45, i.e. matching the CDC's 54%.

Regrettably, this is one's on the FDA, as XBB.1.5 was already on the way out when the FDA chose it. Part of the problem was their desire to include Novavax in the lineup. It has a much longer update turnaround time than Moderna and Pfizer, and Novavax had already committed to XBB.1.5 by the time the 2023 VRBPAC meeting took place.

As for the original vaccine, the waning measurements were in terms of antibody titers, not in terms of actual effectiveness against the target variant. Delta emerged in the spring of 2021, and it had significant immune escape from WT (Wuhan.) By the time the population was immunized against WT, Delta had already driven WT out.

There have not been many reported cases of non-immunocompromised people getting infected with the exact same variant they had been vaccinated against or previously infected with, particularly with WT. There has been too much evolution in the timeline to even dig out the signal.

The original WT mRNA effectiveness measurements were 92-95% IIRC. For all we know, the missing 5-8% might be attributable to immune deficits, early infections, and/or incomplete B-cell maturation. I haven't noticed any research that measured the likelihood of single-variant breakthrough infection, but if you find some I'd like to look at it.

As for other diseases, they are not in the pandemic phase, so their vaccines can be optimized accordingly.

I would dispute that "easily evolve" notion, though. There have been billions of Covid cases since 2019, including countless immunocompromised patients who are basically walking virus incubators. Yet there have only been a handful of major saltations. It's actually quite likely that Covid will eventually be defeated completely.

This is anti-vax misinformation. I don't think actual evidence, studies or data would support this. Let's take a look at real information and refresh our memories.

https://static.dw.com/image/59546575_7.png

https://healthnewshub.org/wp-content/uploads/2021/10/CDCcase...

https://arc-anglerfish-washpost-prod-washpost.s3.amazonaws.c...

https://static01.nyt.com/images/2021/10/28/us/virus-breakthr...

https://static01.nyt.com/images/2022/01/10/briefing/11-MORNI...

I tested positive for COVID last weekend, was out of action for three days and spiked a 40.3C/104.5f fever. It was worse than when I got it three years ago.

I'm not sure if taking e.g. Paxlovid as pre-exposure prophylaxis has been studied, but my guess is that the side effects from the drug are worse in the long run than the disease itself (especially if the seriousness can be blunted via vaccination).

Since people don't spontaneously recover from HIV infection, and the PrEP drugs have relatively few side-effects, the tradeoff is more favorable.

Turns out you can do Covid PrEP with just Neosporin in your nose. It works for other pathogens too:

https://www.pnas.org/doi/10.1073/pnas.2319566121

In case you're wondering, this paper is 100% legit, see e.g. the bio for the big-shot author: https://en.wikipedia.org/wiki/Akiko_Iwasaki

No clue if this easy trick would induce immune escape if a large number of people started using it. I guess it's a good time to get in on the ground floor.

To be a little more precise:

1. "Prophylactic or therapeutic administration of neomycin provided significant protection against upper respiratory infection and lethal disease in a mouse model of COVID-19." 2. "Furthermore, neomycin treatment protected Mx1 congenic mice from upper and lower respiratory infections with a highly virulent strain of influenza A virus. " 3. "In Syrian hamsters, neomycin treatment potently mitigated contact transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)." 4. "In healthy humans, intranasal application of neomycin-containing Neosporin ointment was well tolerated and effective at inducing ISG expression in the nose in a subset of participants."

The mechanism appears to be that Neosporin triggers an ISG[1] (immune) response? Not a biologist etc, but the results showing that it prevents transmission is only in rodent models, and then showing that a similar biomarker shows up in (some of) the participants and the rodent models. They authors say:

> "These findings suggest that neomycin has the potential to be harnessed as a host-directed antiviral strategy for the prevention and treatment of respiratory viral infections."

[1]

Still early in the research, to be sure. Here's the human clinical study:

https://classic.clinicaltrials.gov/ct2/show/NCT05449392

Here's Eric Topol's chat with Iwasaki discussing the finding. Topol's blog may well be the best source for Covid research out there:

https://erictopol.substack.com/p/akiko-iwasaki-the-immunolog...

This paper gets ripped into in my favorite podcast, TWiV (This Week in Virology)!

Essentially, yes, neomycin in the nose, if timed perfectly, can activate the innate immune system, but en mass this practice would cause the spread of antibiotic resistance.

Link: https://podcasts.apple.com/us/podcast/this-week-in-virology/...

If it turned out to work great in practice and people started using it en masse, the benefits would greatly outweigh the costs IMO, particularly if it snuffed out Covid and/or the flu. If it ends up being a niche thing, I doubt it would bite into the resistance numbers.

Besides, we're already spiraling down the resistance chasm with antibacterial soaps, stuffing cattle with antibiotics, overprescribing, and so on.

You don’t even need that. Carrageenan works: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493111/

Obviously it’s not stimulating the immune system but it works as an antiviral barrier. I’ve been using it since I read that study and I’ve avoid 2 of my daughter’s colds since (and still got 3). That might not sound impressive but I have a terrible immune system and haven’t avoided a cold from someone I’ve had close exposure to in as long as I can remember.

That said, I might need to add some Neosporin to my mixture when she comes home with her nose running.

Do you buy a premade nasal spray with carrageenan or make your own somehow?

I make my own. There's at least one product out there but it's something like $20 a bottle and you can make it for pennies. Here's a recipe:

For 150ml of (distilled) water: 1.35g of salt 1.8g of iota carrageenan A drop of polysorbate 20

Heat up the water to close to boiling, add those things, shake it up, and there you go.

Note: That was supposed to be in line with the product that was tested, but I've found adding more water makes it come out of the nose spray bottle thing better. It's still pretty thick, just not a complete gel. Perhaps there's another type of spray bottle that would be better.

In the long run, the side effect of HIV is death due to total collapse of the immune system.

This injection isn't a vaccine, it's an anti-viral drug being used as pre-exposure prophylaxis. The first approval of this approach was in 2012, but using an oral pill with a short half-life taken daily.

That drug is still in use and also highly effective, the new improvement is to provide the same approach with a longer acting injected drug. One reason there has been great interest in this, despite the already effective oral PREP, is that there are thought to be socio-behavior advantages for cases like women in Africa as in this study. For example: the woman does not have to keep a supply of daily pills that a partner can find. Also possibly improved adherence with no missed doses.

The drug itself is not thought to be more biologically effective than the oral drugs, which are basically already at close to 100% effective assuming the patient actually takes them as scheduled.