There was one study that saw 0 participants who contracted HIV during the trial according to the data on the FDA PDF [0]. Was 2,000 participants in Africa who were identified as potentially at risk, aged 16-25.
> YEZTUGO demonstrated superiority with a 100% reduction in the risk of incident HIV-1 infection over TRUVADA (Table 13).
~2,000 given YEZTUGO with 0 infections by the end. ~1,000 given TRUVADA with 16 infections by the end.
Now, this is a great study result if accurate. Substantially better. However, 100% protection is misleading clickbait article. The company does not claim to be 100% effective anywhere I can see... and at best they lifted this statement from this study to use as clickbait.
0: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/22...
Another had 2 participants contract HIV out of about 2000 "Person-years". This was compared to another HIV treatment where 9 people contracted HIV (with only 1k "person-years" in that cohort). This equated to 89% reduction in HIV contraction compared to the other PrEP drug.
And that IS a fantastic result and if everyone could take this we'd probably be in a great spot HIV wise. ~90% improvement over current PrEP is great, and it's way easier to take and not mess up.
[1] https://www.askgileadmedical.com/len4prep/understanding/#stu...
people magically get more vigilant is as leakly as virus magically goes away on its own.
"Efficacy" is how well something works under ideal conditions.
"Effectiveness" is how well something works in the real world.
So yes - "This is more effective because adherence is easier" is both true and intended.
Having grown up when AIDS was peaking, the idea of this scourge preventable and treatable feels damn near like sci-fi, and I’m thrilled at the progress we’ve made.
As a data point, the paper below shows 1,213 out of 18,401 high-risk people in France got infected in 4 years (and 260 out of 31,992 with the previous gen prep, it seems this one reduces it by ~10x again)
https://www.thelancet.com/journals/lanpub/article/PIIS2468-2...
What a medical miracle, seriously!
How long would it take for a drug with this level of protection to result in ~no cases of HIV? What level of adoption would it require?
>if a certain event did not occur in a sample with n subjects, the interval from 0 to 3/n is a 95% confidence interval for the rate of occurrences in the population.
They cite 99.9%, and “reduce the risk”, not 100% like this sub article claims.
https://www.gilead.com/news/news-details/2025/yeztugo-lenaca...
In the same article we go from:
> The first 100% effective HIV prevention drug is approved and going global
to a couple paragaphs in:
> sold under the brand name Yeztugo – a class of drugs known as capsid inhibitors, which provide almost 100% protection against HIV infection
To a little bit later:
> The pre-exposure prophylaxis (PrEP) provides HIV-negative individuals around 99% protection from contracting the devastating virus through sex.
So... that is terrible writing about a topic like this.
From what I have seen there is no difference in effectiveness of this drug compared to the pills we already have if you actually take them properly.
I would love to be proven wrong, but this seems basically the same efficacy numbers we see for truvada and descovy.
That doesnt mean it is not still valuable, properly taking the pill every day is a huge component of that. I know I plan on looking at the shot personally.
But the reporting on this article is extremely shady.
https://www.researchgate.net/publication/262227835_Concerns_...
I wonder what this will look like worldwide, especially in countries where this is needed the most, once production ramps up.
https://www.aaas.org/news/road-lenacapavir-breakthrough-hiv-...
Seems to be a combination of university funding (University of Utah), big pharma (Gilead), and global HIV advocacy groups working together.
Sadly this kind of university research and non-profit advocacy groups are both prime targets of the Trump administration’s funding cuts. The next breakthrough drugs may have to be developed in some other country.
https://en.wikipedia.org/wiki/Gilead_Sciences#Pricing
Gilead came under intense criticism for its high pricing of its patented drug sofosbuvir (sold under the brand name Sovaldi), used to treat hepatitis C. In the US, for instance, it was launched at $1,000 per pill or $84,000 for the standard 84-day course, but it was drastically cheaper in the developing world; in India, it dropped as low as $4.29 per pill.
Low priced HIV drugs for the poor is part PR and part pragmatism. Poor people can't pay the sorts of drug prices that insured Americans do, and poor countries aren't going to enforce drug patents purely for the benefit of American corporations, e.g.:
https://en.wikipedia.org/wiki/Medicines_and_Related_Substanc...
Gilead looks gracious by preemptively embracing the situation that was going to occur anyway (poor patients aren't going to pay high prices).
IMHO this is great - broadest shoulders shoulder most.
However, it likely should be more organized? Maybe do more of this research in public institutions and make it freely available to commercialize.
Which becomes annoying when fairly rich Europeans ride these coattails (and defense) while being incessantly snobbish about their healthcare superiority, in large part paid for by us.
Though a big part of the Trump win comes from this - yea some Americans are rich, but a lot of them are really poor and justly mad at how much more expensive things are that we produce.
The EU’s Horizon Europe is €95.5B (2021–27) with €16B for ERC alone, national funders like the UK’s NIHR spend ~£1.4B/yr, and Europe’s pharma industry invests ~€50B/yr domestically.
Europe is home to Roche, Novartis, AstraZeneca, Sanofi, GSK, Novo Nordisk, each spending billions annually on R&D (Roche CHF 13.2B, AZ $13.6B, Sanofi €7.4B etc.). Also a big chunk of US list‑price "overpayment" never reaches manufacturers—rebates/discounts were an estimated $335B in 2023—so it’s not all subsidizing innovation.
Innovation is now multipolar: in 2024 more NAS originated from China (28) than from the U.S. (25) or Europe (18). So strong US funding matters, but Europe clearly pays and builds a lot too.
That said, our ... fascinating ... experiences ... in trying to get the government to fix our health systems is certainly no outsider's fault. Europeans and others can feel at ease continuing to mock us.
I'm 63, and my wife is near my age. We take this stuff seriously.
I have known many people that have been completely devastated by medical crises. Even with insurance, some types of illness can be catastrophic, financially.
I also have known quite a number of folks that have done an amazing job of taking care of themselves, yet still had medical crises.
-but if I get a terminal, especially long-term illness, it's a wipeout either way; if I'm out $20k/year to the healthcare providers and $20k/year to the insurance company, and can't work -- draining $40k/year in health costs just isn't going to work out for very long, unless I can make it another decade or two.
Edit: I should say, too, I give money directly to my daughter (that is, well before [ideally] I'm ill), specifically so I can declare bankruptcy with less family wealth loss if I should have to, and to help fend off Medicaid clawback.
But $84k seems a little pricey. Imagine paying that out of pocket.
I hate this so much. Nobody knows how much anything costs. What kind of market is this?
1 - Premium
2 - Co-Pay
3 - Deductible
4 - Co-Insurance
5 - Balance Billing
6 - Non-covered items
Slightly off topic, but I have this exact feeling every time I visit the US and buy stuff in a store.
"Sorry, we don't include tax in the price that is displayed, so you'll need to either figure that out in your head or just pull the slot machine of what you are actually gonna pay at the register."
And don't give me the "taxes are different from place to place" cuz the store ain't gonna change place while I am in it. So much is just psychological warfare in the US, which just has no reason to be...
It's not as though most people are in a position to shop around when it comes to tax authorities.
This is a hugely underappreciated aspect of why the cost of health care, including insurance premiums, is so high in the US. Well-meaning folks have called for decades for the US to transition to single-payer, citing the overall lower cost experienced in other countries as a primary motivator. Meanwhile, US companies remain the global leaders in the development of pharmaceuticals and medical equipment. That development is often subsidized by US taxpayers and the remainder is largely recovered from US patients because the single-payer systems in other countries often impose price controls that largely don't exist in the US.
(This is not meant to argue against single-payer in the US. All things being equal, a single-payer system would likely solve many more problems than it would cause. I'm just pointing out what many before me already have about how Americans disproportionately subsidize the development of the healthcare the rest of the world benefits from).
Or, just fund government research endeavors with no profit motive. If we can have a JPL for aerospace engineering, why not for pharmaceuticals?
I mean China is really rich, runs lots of centralized R&D, and has an excellent research culture, why isn’t it developing cures for everything?
The US has enjoyed a high concentration of R&D talent and funding which has somewhat starved out the desire of the rest of the world to do similar research.
If you are China, for example, why spend the funds to R&D new drugs when you can pull the same research from NIH and FDA efforts of the US and produce those same drugs for cheap.
And that isn't to say China is the only nation doing this. India is pretty famous for doing the same thing.
The issue with these drugs is once the chemical structure is known and proven to work, it's (usually) relatively trivial to spin up manufacturing.
China puts in R&D on products that are hard to manufacture even if the "how" is well known. They do that because China is a country built on international trade. That's why they are a world leader in battery tech.
Boner pills? Sure, go nuts on patenting those. But HIV prevention? No, it's immoral to patent this.
That has not been the case at all in the countries that did go that route. The US system has serious issues but I would take it over Canada's any day.
Citation needed. The US is neither dominating the list of big pharma (see e.g. Novartis, Roche, Astrazenica...), nor are the US exceptional in R&D spending per GDP (South Korea and Israel are the outliers). https://ourworldindata.org/grapher/research-spending-gdp?tab...
From the first link in the OP you're replying to:
> The United States Senate Committee on Finance launched an 18-month investigation of Gilead's Sovaldi pricing, and argued in its 2015 report that Gilead set prices high in disregard of the human cost and in order to set the stage for a higher eventual price for Sovaldi's successor, Harvoni. The committee's investigation, based in part on internal documents obtained from Gilead, revealed that the company had considered prices ranging from $50,000 to $115,000 per year, trying to strike a balance between revenue and predicted activist and public relations blowback, with little regard to research and development costs.
The pricing was found to be intentionally divorced from R&D costs. They are charging as much as they can because they can, not because of R&D.
It's fascinating that "fair" ends up being that the drug developer has to capture the correct amount of the value they are providing the patient, and the patient gets the rest.
Keep in mind that the value is only "theirs" by force of IP law which at least officially exists for the benefit of society as a whole. Permitting a situation where people are priced out of a cure because the only available alternative is exorbitantly expensive doesn't seem moral or useful.
If the concern is ensuring corporate investment into R&D then public policy could be adopted to subsidize R&D expenses either up front or after the fact.
No denying the US plays a huge role in the global pharmaceutical industry - but Europe does too - semaglutide (Ozempic/Rybelsus/Wegovy) was developed by Novo Nordisk, headquartered in Denmark.
The popular ADHD drug lisdexamfetamine (Vyvanse/Elvanse) was developed by a US-based research team, but they ended up being acquired by a British pharmaceutical company (Shire), which in turn was acquired by a Japanese company (Takeda), who owned the patents (which expired last year or the year before, depending on country), and remain one of the major manufacturers of it.
If you want a career in drug development, there are huge opportunities in the EU and Switzerland; by no means are you limited to the US. As usual, in the US you will almost certainly get paid more, but some people find the social setting of Europe more to their liking, and view that as a compensating advantage which makes up for lower pay.
- *For many large pharmaceutical companies ("Big Pharma"), marketing costs often exceed R&D spending.* In analyses of the top 10 drugmakers by revenue in 2020, 7 companies spent more on sales and marketing than on research and development. For example, Johnson & Johnson spent $22 billion on marketing compared to $12 billion on R&D; Bayer spent $18 billion on marketing vs. $8 billion on R&D[1][2].
- The combined marketing spend for these top 10 companies exceeded R&D by $36 billion (about 37%) in 2020[1][2].
[1] https://www.ahip.org/news/articles/new-study-in-the-midst-of... [2] https://www.csrxp.org/icymi-new-study-finds-big-pharma-spent...
Well, fuck that. I'm already paying $24K annually for my health care that covers about half of anything short of a catastrophe.
I'm not an expert on this, but my PBM insists on going with stores that have higher prices. If I go with the less expensive store, they do not cover it. Sometimes, it makes sense to co with the less expensive store, but then it doesnt even draw down your annual deductable. Damned if you do, damned if you dont.
Seeing that pharmaceutical companies, on average, spend much more on marketing than R&D I would eliminate marketing.
Most of the rest of the world has banned drug advertisements, and sales reps whose activities more resemble bribery than anything else, and they're doing fine.
Don't even eliminate it. Just halve it. The typical drug "researcher" spends $2 on commercials and sports sponsorships for every $1 spent on R&D.
In addition to marketing, pharmaceutical companies spend, again on average, MUCH MUCH WAAAAAAAAY more on stock buybacks and dividends than they do R&D. Between $2 and $4 for every $1 spent on R&D.
That could also be a source of, oh who the hell am I kidding...
Modern drugmakers aren't biotechnology companies, they are financial instruments that just so happen, by coincidence, to employ chemists.
The obvious objection is that this will result in inflated research budgets and maybe marketing-adjacent research (like benchmarking). But actually, more benchmarking could be good. Or maybe they’ll inflate their research budgets by dropping money into basic research.
I expect that in many cases this is only true because the advertising market is competitive - you can’t advertise less, or you’ll lose market share to your competitors. But if everyone is prohibited from advertising cars, is the total market for cars really going to shrink? And if it does, is that actually a net negative for society?
Anyway, marketing is a useless overhead in our society for the most part. Especially in the case of medical products, where you go talk to a professional, a doctor, who can recommend the ones you actually need.
“To what end,” my goal is to at least pin it to something that might have useful side effects, R&D.
Stock buybacks and dividends are basically just a proxy for profits, and the fact that a company has greater profits than R&D spending isn’t a ratio that’s especially meaningful.
(You could, however, make a good argument that if profits are too high, it’s an indicator that the market isn’t adequately competitive, and regulation or anti-trust enforcement is merited to ensure competitiveness.)
Btw, nothing on the article about potential side effects.
In the US, there are certain patients who are at high risk for HIV infection. They are men who have sex with men, intravenous drug users, and people who have sex for money or housing.
In Southern Africa, young women experience some of the highest incidence rates of HIV infection in the world [0], so that would be the high risk population there.
In terms of side effects, there are practically none for the once-every-two-months drug Apretude, which is prescribed in the US for the high risk population I mentioned. They are mostly around the physical injection itself/
This is not a vaccine, BTW, and it needs to be given every 6 months.
The redundancy on a bacteria is degrees higher than on viruses which are extremely efficient so they're more prepared to survive if that were to happen. But it also depends on the way you're doing the drug.
That doesn't mean virus can't adapt, they do. But if you manage to hit the right pieces it might just not be possible for them to do so fast enough. Obviously finding that particular protein and figuring out a mechanism to target it while at the same time for your drug not to have undesirable side effects on the host is an expensive, long and difficult process.
For this drug in particular, it doesn't function the same way PrEP does; this targets a different protein which previously was thought to be too difficult to target but new research on it showed that perhaps there was an easier way to do it and that's how this drug (lenacapavir) came to be. However that was not the end of the story as there was also a problem on how to actually deliver the drug to the cells as the drug is relatively insoluble and isn't easily absorbed by the body so although the drug was promising when it comes to affecting the virus it didn't seem to be possible to develop a drug that could be deliverable to people. Eventually though they did figure this part out and that's how we got where we are.
But generally, to answer your question, finding the right molecule to target; a right way to target it and a right way to deliver it is really the problem when it comes to drug development, being so targeted and specific makes it extremely unlikely for the virus to develop a resistance because it would mean it has to become a whole new virus basically.
correct that it isn't over because of this potential, but the way this one works is by targeting the capsid
the body's immune system goes after infected cells based on the coating and signature of those cells. HIV and retroviruses replicate far too quickly for our immune system to follow along, as well as experiencing rapid selective evolution within our body that eventually in nearly all scenarios results in complete immune deficiency, where the body no longer recognizes the cells as infected because they both blend in, while another population has exhausted the immune function as the body continues to fight too many infected cells. This is the AIDS part of HIV. The iteration takes a predictable amount of time to occur, but they are convergent evolutions in everyone's body.
by targeting the capsid specifically, this is destroying the container for HIV's RNA before it gets to a cell at all
this should be an evolutionary dead end, only controversial to say because its been 44 years of this, but should gain confidence in the future
So if a patient is exposed to HIV while on the drug, this will not prevent their cells from being infected with the virus. The infected cells will not subsequently create any virus, and therefore additional cells will not be infected, however nothing prevents actual exogenous HIV from infecting cells while on this drug.
That means that if someone discontinues the drug, cells that have been infected with HIV during the time they were on the drug can start producing it causing AIDS.
It’s great that there’s a drug that works as well as this for chronic use, but nobody should think that it’s actually preventing infection. It’s allowing infection but inhibiting viral replication post infection.
That being said, Wikipedia doesn’t really agree with your mechanism. See:
https://en.m.wikipedia.org/wiki/HIV_capsid_inhibition
It seems that the drug may inhibit disassembly of the capsid.
I think, though, that the underlying assumption is that the old virus hangs out, forever waiting for the moment to strike.
Cells senesce and die and get replaced, and the immune system is always active in the background. If the virus particles are released, the immune system is going after it and cleaning up. As essentially no new virus is being created, this is the body's opportunity to clear the virus at a slower, manageable pace where it doesn't have to contend with a rapid, expanding infection.
It feels like one of those ideas that's technically true in all the right ways, but misses one crucial piece that would make the whole thing accurate.
If this really applied to HIV, then people with HIV who take effective antivirals for long enough would be cured. But they generally aren't.
Assuming GP is correct, from other comments it sounds like that’s in question.
I would love to sit in on branding meetings for pharmaceuticals.
Sure, vaccinating high risk sexually active preteens in regions of Africa will dramatically reduce infection in ways that have been insurmountable to those on the frontlines.
But for everyone else, this doesn't seem to materially change anything.
A sexually active adult or accidental/intentional polycule in western nations has no change in user experience. The risk remains both low and essentially the same. Test often if you are in "sex-positive" communities where testing and sharing results isn't taboo. Or do nothing and just imagine you're being responsible. Its the same as before.
PreP users can switch to a 2x yearly regime instead of the current frequency, but that's only for people with partners already.
I just don't see this as good enough unless it turns into like a one time vaccination, done as part of a cocktail in a normal routine checkup.
If we did, we could end a lot of suffering in a decade or two for many at risk people.
gschizas•10h ago
pkulak•10h ago
> provides HIV-negative individuals around 99% protection from contracting the devastating virus through sex
randcraw•10h ago
You'll note also, the sole source for the article is Gilead (mentioned at the end), the drug manufacturer.
freeone3000•10h ago
For pricing, Gilead will likely carry over its policy for Truvada, by charging fairly high rates to western countries (with vouchers available) to subsidize its operations in Africa, where it will be provided cheaply or freely.
(Disclosure: I’m an investor. I truly believe that if any company can be morally good, Gilead qualifies.)
https://www.gilead.com/news/news-details/2024/gileads-twice-...
https://www.gilead.com/news/news-details/2025/gilead-finaliz...
https://www.gilead.com/news/news-details/2025/gilead-receive...
haswell•8h ago
The primary reason Gilead exists in my memory is the headline years back about their exorbitantly high prices for a life saving hepatitis C drug and the resulting questions this was raising in congress ($84K for a 12 week supply) [0].
While it may be admirable that they are providing these drugs freely to countries in need, I’d be more hesitant to accept at face value the claim that US prices in particular are somehow reasonable on that basis. I also question the framing that those high prices are necessarily high. I’m less familiar with how they’ve priced things in recent years.
- [0] https://news.ycombinator.com/item?id=7529435
wbl•8h ago
freeone3000•47m ago
ksherlock•10h ago
In 2024, lenacapavir was named the "2024 Breakthrough of the Year", citing its "astonishing 100% efficacy" in one large efficacy trial in women to prevent HIV and "99.9% efficacy in gender diverse people who have sex with men,"
https://en.wikipedia.org/wiki/Lenacapavir
It's curious that the article (and wikipedia) specifically refer to sexual acquisition.
aerostable_slug•9h ago
They may also have issues trying to conduct robust clinical trials with IV drug abusers. If a subject entered rehab or were incarcerated for a period of the trial, would that invalidate their data? I don't know enough about the subject but it intuitively feels like it could present a real challenge.
pitpatagain•9h ago
42772827•8h ago
Yes, and people who take IV drugs are much less likely than men who have sex with men in general to take a pill daily.
kstrauser•8h ago
In the 90s, some STD training I took said it was highly unlikely for otherwise healthy bio women to contract HIV from a man (ie compared to sex trafficked women in poor health), with the claim that vaginal sex is less susceptible to micro tearing that allows easy transmission than anal sex is.
I didn’t really question this at the time because it seemed plausible and I believed the people who were telling us this. (Note: this was in a medical context, not someone trying to scare us.) Is there any credibility to that idea now that we have more data, and hopefully leased biased science than we had in the 80s?
lukeschlather•8h ago
https://stanfordhealthcare.org/medical-conditions/sexual-and...
https://pmc.ncbi.nlm.nih.gov/articles/PMC3412216/
kstrauser•7h ago
badlibrarian•6h ago
> The analysis, based on the results of four studies, estimated the risk through receptive anal sex (receiving the penis into the anus, also known as bottoming) to be 1.4%.
> It is estimated the risk of HIV transmission through receptive vaginal sex (receiving the penis in the vagina) to be 0.08% (equivalent to 1 transmission per 1,250 exposures).
lukeschlather•2h ago
badlibrarian•33m ago
05•6h ago
[0] https://stanfordhealthcare.org/medical-conditions/sexual-and...
GuB-42•8h ago