All aside from the healthy criticism on the clickbait title, I found the approach to make it royalty-free (presumably for generic production) and free of cost access to uninsured individuals incredibly fascinating. How will they manage to cover R&D costs? That’s the primary reason pharmaceutical companies use to justify exorbitant drug prices. Was this a result of a philanthropic endeavor?
philipkglass · 18h ago
It was developed by Gilead Sciences, Inc. The way they can afford to make it cheap for people who can't pay is by charging high prices for insured Americans. You can see this with their earlier developed treatment for hepatitis C:
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.:
Gilead looks gracious by preemptively embracing the situation that was going to occur anyway (poor patients aren't going to pay high prices).
oldandboring · 18h ago
> The way they can afford to make it cheap for people who can't pay is by charging high prices for insured Americans
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).
heavyset_go · 16h ago
> 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.
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.
maxerickson · 14h ago
$84,000 for a (likely) cure is a huge improvement over ~$300,000 for a liver transplant. This is partly how they established the pricing, they knew that insurers would go for the cost savings.
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.
fc417fc802 · 12h ago
> 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.
maxerickson · 12h ago
Maybe IP law was a subsidy all along.
markdown · 9h ago
The price to the recipient of a liver transplant in India is USD$20k to $35k.
There's no good reason a liver transplant should cost 300k, so yours is a false comparison.
f1shy · 7h ago
Did you read the comments? OP is comparing costs in USA. The cost of the drug in India is much less
0xDEAFBEAD · 6h ago
I don't think that affects the GP point though. If the US is a profit center for pharma, that makes developing drugs more profitable overall, which means more drugs will be developed.
Pharma companies are gamblers. They gamble on the cost of R&D, the market size for the drug, the amount they will be able to charge. The higher the expected value of their profits, the wider variety of drugs look like attractive prospects financially.
skissane · 13h ago
> Meanwhile, US companies remain the global leaders in the development of pharmaceuticals and medical equipment
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.
jjani · 8h ago
> As usual, in the US you will almost certainly get paid more
Switzerland is one of the few countries where getting paid more in the US for the same job would generally not be an "as usual" :) The large majority of equivalent jobs gets paid more in Switzerland, including office ones. The ones that don't are the outliers (which are of course greatly overrepresented here on HN).
This is IME, so feel free to correct me if I'm wrong.
spjt · 11h ago
As a former pharmaceutical chemist, the job market in the US is kind of shit, which is why I write code for a living.
0xDEAFBEAD · 5h ago
Novo Nordisk charges about 10x as much for Ozempic in the US as it does in the EU:
As long as they spend so much on marketing, it's hard to believe them when they say the only way they can recoup their R&D investments is to charge high prices.
- *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].
Imagine how much cheaper healthcare could be if the US simply banned direct to consumer drug advertising.
Surely that's something that would be easier to get bipartisan support for, somewhat avoiding the "socialism vs capitalism" chasm between the parties that prevents meaningful healthcare reform.
LargeWu · 17h ago
I think there's a case to be made for incentive programs for development of key drugs, akin to the way Operation Warp Speed operated for the COVID vaccines. Provide up-front cash for initial research and large guaranteed returns if a drug is approved; in exchange, the drugs become public domain.
Or, just fund government research endeavors with no profit motive. If we can have a JPL for aerospace engineering, why not for pharmaceuticals?
doctorpangloss · 17h ago
The status quo is bad, but do you have any evidence for drug development anywhere else in the world, that plays by the rules you’re describing?
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?
cogman10 · 16h ago
It's a little bit like the state of chip fabrication.
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.
nxobject · 16h ago
After the latest round of research cuts to basic biomedical research and hostility towards foreign academics, why not give it 10 years? That's how long it'll take for the current cohort of graduates to find the institutions they'll stay in long-term.
scroogey · 16h ago
It takes time to develop institutions and foster the talent, but China is certainly advancing at a fast pace: https://archive.is/Csvbe
LargeWu · 11h ago
I guess my point of view is, truly game-changing pharmaceuticals should be shared with the world. And there's precedent for that. Jonas Salk did not patent the polio vaccine he discovered, and the world is a better place for it.
Boner pills? Sure, go nuts on patenting those. But HIV prevention? No, it's immoral to patent this.
CommenterPerson · 15h ago
What are the development costs for Insulin, discovered 100 years ago? Americans overpay not to subsidize others but because Pharma Bros.
selectodude · 15h ago
Newer insulins are pretty insane in how they work. Insulin icodec, for example, basically eliminated the need to set basal dosing because it's a once-weekly injection. Insulin is cheap. The newest, best, most convenient insulins are expensive.
phanimahesh · 2h ago
I've heard even the plain old insulin is significantly more expensive in US compared to Europe.
vjvjvjvjghv · 16h ago
The US taxpayer is mostly subsidizing stock buybacks.
cycomanic · 16h ago
> 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.
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...
the_d3f4ult · 15h ago
Neither of the things you mention detract from his point. Just because the companies are headquartered outside of the US doesn't mean that they aren't developing drugs with the intention of recouping their R&D costs (and then some) from the US market due to our uniquely broken healthcare system.
jsbg · 16h ago
> All things being equal, a single-payer system would likely solve many more problems than it would cause.
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.
No comments yet
tossandthrow · 18h ago
Privatized progressive tax?
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.
0xDEAFBEAD · 5h ago
>broadest shoulders shoulder most
Part of the reason the US has a higher GDP is because we work longer hours and take less vacation. "You work harder, therefore you should shoulder more" hardly seems fair.
Europe makes fun of us for our defense spending yet demands protection, makes fun of us for working long hours yet says we should shoulder more, makes fun of us for overspending on health care yet charges us 10X as much for the drugs they manufacture: https://www.healthline.com/health-news/heres-how-much-more-o...
I just can't shake the feeling that Europeans see Americans as suckers.
fnordian_slip · 3h ago
Just in case you are interested in a European perspective, and aren't just commenting to let off some steam because of perceived injustices:
> we work longer hours and take less vacation.
Yes, but people working longer hours doesn't necessarily translate to more output, especially when quality is taken into account.
Anecdotally, from what I've heard from people working in international companies, the American work culture doesn't seem to be very efficient when looking at the end result. The studies of 32 hour work weeks seem to indicate similar findings, though like the anecdotes, should be taken with a grain of salt of course. But I truly believe that in most cases, a developer who works 10 hours a day will not produce more than one who works 6 hours a day, at least after a couple of days.
>Europe makes fun of us for our defense spending yet demands protection
You do realise that until very recently, America has gained an absurd amount of soft power through this defence spending, right? And was able to convert this soft power into a lot of GDP through indirect subsidies of its international companies? Just because the current administration has squandered this advantage, doesn't mean you did not get out more than you paid for the last couple of decades.
>I just can't shake the feeling that Europeans see Americans as suckers.
I agree with you on that point,but not for the reasons you might think. I see the "temporarily embarrassed millionaire" phenomenon, people constantly against their self-interest and the like, and and it's hard not to. I have relatives in the US, and I still feel sympathy for your people.
But it's getting harder and harder to not see you as suckers when you look at the tariffs or the cuts to welfare, science and education, all while the rich get massive tax cuts. And all is being done in the name of "draining the swamp", by a billionaire who is incredibly well-connected with 90% of the corrupt elite he publicly opposes.
nwienert · 17h ago
It's been like this, Americans heavily subsidize the world in healthcare/research.
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.
kldg · 16h ago
Since a year or two before the individual mandate ended (it was worth the fee), I dropped health insurance and self-pay for self and family; I pay now in a year for actual service what I paid in a month in premiums, mostly to dentist, without feeling any restrictions on seeking healthcare. I don't often need referrals, can self-order procedures directly, and the amount insurance says they "negotiated" is pretty misleading, often comparable to what I pay in cash without insurance. Since ACA was implemented, prior to covid, life expectancy in the US stopped increasing; not to say ACA is directly responsible (without more data), but whatever its net benefits may be are clearly losing out to other signals.
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.
ChrisMarshallNY · 15h ago
Ooohh... Wait until you have a really nasty health emergency.
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.
kldg · 12h ago
It's a lottery either way, I think. I can pay $20k/year for health insurance and limit to $20k/year in expenses (or w/e current annual limit is), or I can save the $20k/year and put it into an unencumbered investment account. The insurance company charges so much that I feel much better about getting out of insurance in my 20s so that I have a pretty decent pile now in my 30s, and going forward, the pile accumulates as my risks do.
-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.
lossolo · 16h ago
US carries a big share of the biomedical load, NIH runs ~$48–50B/yr and the US is the launch market for 2/3 of new‑drug sales, which makes it the main revenue engine, but calling Europe a freeloader skips a lot of facts.
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.
bee_rider · 18h ago
I don’t mind regional pricing, I mean, supply and demand works out differently in different markets, right?
But $84k seems a little pricey. Imagine paying that out of pocket.
42772827 · 18h ago
Nobody pays that. It's a pre-negotiation price that exists as a factor of many other costs and payments to various stakeholders like PBMs.
vjvjvjvjghv · 16h ago
“Nobody pays that”
I hate this so much. Nobody knows how much anything costs. What kind of market is this?
NekkoDroid · 14h ago
> Nobody knows how much anything costs.
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...
fc417fc802 · 12h ago
Sure that mildly annoys me but does it really matter? Everything in the store is taxed according to the relevant laws for the region. It's not as though this TV will have 10% tax but that TV will have 50% tax. They'll both be taxed according to the item category they fall under.
It's not as though most people are in a position to shop around when it comes to tax authorities.
vjvjvjvjghv · 12h ago
It would be nice to know how much something costs before you pay.
cm2012 · 9h ago
Americans just do the quick math for their locale for taxes, not nearly the same thing as opaque medical fees.
beAbU · 6h ago
The entire rest of the world has figure out how to include tax in the label price of items on retail store shelves.
bee_rider · 12h ago
It’s just dishonest, and it makes it difficult to guess how much you are spending before you get to the register.
vjvjvjvjghv · 12h ago
Don't forget to add the ever increasing expected tip in ever increasing number of venues.
bobthepanda · 14h ago
Health insurance in the US is specifically mostly not a market, because your employer picks your health insurance for you.
TuringNYC · 10h ago
Also, markets are supposed to have associated prices. In US healthcare you learn the price later, sometimes weeks or months later, in the form of balance billing. For those not in the US -- you pay six ways:
1 - Premium
2 - Co-Pay
3 - Deductible
4 - Co-Insurance
5 - Balance Billing -- you dont learn the full cost until weeks/months later
6 - Non-covered items -- you dont learn the full cost until weeks/months later
limagnolia · 11h ago
But if they are offering royalty-free production to generic manufacturers, why wouldn't insurance companies simply insist on using the cheaper generic?
TuringNYC · 10h ago
>> But if they are offering royalty-free production to generic manufacturers, why wouldn't insurance companies simply insist on using the cheaper generic?
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.
ninetyninenine · 10h ago
This drug is cheaper if you don't buy insurance? What?
CodeWriter23 · 13h ago
> The way they can afford to make it cheap for people who can't pay is by charging high prices for insured Americans
Well, fuck that. I'm already paying $24K annually for my health care that covers about half of anything short of a catastrophe.
42772827 · 18h ago
They bill the insurance companies a lot, plus they take public and private (i.e., government and Gates Foundation) investment.
erikig · 14h ago
A quick online search revealed that the HIV prevention drug Yeztugo (lenacapavir), is priced at $28,218 per year in the US. This translates to $14,109 per injection, as it is administered twice a year.
I wonder what this will look like worldwide, especially in countries where this is needed the most, once production ramps up.
spjt · 11h ago
Would be nice if I could just directly get paid $28K/year to not have sex.
pavlov · 18h ago
Here’s a detailed account of the development spanning over thirty years:
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.
os2warpman · 18h ago
>How will they manage to cover R&D costs?
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.
Marsymars · 18h ago
> 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.
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.)
bee_rider · 18h ago
It would be kind of interesting to require companies to limit marketing budgets to half of R&D, or whatever.
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.
nineplay · 18h ago
To what end? Companies spend $X on marketing to make $X + $Y. If you force them to reduce $X than assuming they don't come up with creative financial workarounds, you've just made them make less money. What has this accomplished for the betterment of anyone?
Marsymars · 18h ago
> To what end? Companies spend $X on marketing to make $X + $Y.
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?
bee_rider · 17h ago
I don’t think that is the model they use, it is too over-simplified to say anything.
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.
ldoughty · 20h ago
"Lies, ** lies, and statistics"
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.
Yeah, it's not 100% protection in all studies. One study did have no participants contract aids which is fantastic and would be one data point for 100% prevention.
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.
What’s a typical rate for infections per person-year among people not using these precautions? For those who don’t know follow the epidemiology here, how good effective are the older drugs compared to not taking them?
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.
okaram · 17h ago
This heavily heavily depends on the population you choose, given the difference in sexual habits.
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)
Thanks for that! So yeah, by that, existing PrEP is very effective, and this new one is much better yet.
What a medical miracle, seriously!
pitpatagain · 19h ago
I think it's pretty clear that being easier to take and not mess up is the reason for the difference in statistical effectiveness. The reason for lower numbers for effectiveness of daily oral Truvada prep is primarily measuring differences in adherence.
Fomite · 18h ago
We actually have terms for this.
"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.
Ericson2314 · 18h ago
Just so where clear, from a public health as opposed to basic science standpoint, that's a distinction without a difference.
people magically get more vigilant is as leakly as virus magically goes away on its own.
pitpatagain · 15h ago
Yes, my phrasing was responding to the way the parent stated it as "90% more effective, and also it's easier to take". As you say: It's 90% more effective precisely because it's easier, not and also. Behavioral factors matter an enormous amount for the real world success of many types of drugs!
MostlyStable · 18h ago
I'd be interested in a modeling study looking at the equilibrium infection rate, assuming everyone was on the drug, but otherwise did not change their behavior with regards to risky sex (or maybe even under a few scenarios of increased risky behavior from risk compensation [0]. You don't actually need 100% protection for the longterm equilibrium to be eradication of HIV (that's the whole idea of herd immunity).
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.
SamuelAdams · 17h ago
The cited article is a better source, and it was written a month ago. I am not sure why this is making the rounds now.
They cite 99.9%, and “reduce the risk”, not 100% like this sub article claims.
First, on the article itself. That title is just misleading clickbait.
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.
cguess · 19h ago
The difference is it's twice a year injection, not daily or monthly pills. For many at-risk populations (unhoused, people living in the rural developing world) taking a pill once a day, or even monthly, much less making you can refill your prescription is insanely difficult.
duskwuff · 15h ago
There's an ugly social aspect to it, too. In South Africa, for a woman who is in a relationship to take PrEP is often seen as an admission of her infidelity.
The problem with this drug is that it inhibits one of the final stages in viral replication. This means that before it can work the virus has already infected the cell and added its RNA to the host cells DNA permanently.
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.
amluto · 16h ago
This sounds like a sort of plausible mechanism, but do you have any actual evidence that this occurs in real life? I admit that I’ve wondered whether the PrEP studies with lenacapavir actually measure what they thing they measure given that the same lenacapavir may prevent HIV from replicating enough to be detectable.
That being said, Wikipedia doesn’t really agree with your mechanism. See:
It seems that the drug may inhibit disassembly of the capsid.
brianleb · 15h ago
Agree that it sounds 'close to correct.'
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.
amluto · 14h ago
> 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.
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.
> The medication works in two ways: First, it interrupts viral replication by preventing HIV from reaching the nucleus of an infected cell, which then blocks reproduction.
> The second mechanism is for cases in which integration of the HIV genome has already occurred. In this instance, lenacapavir interferes with production of viral progeny
In other words, it has multiple mechanisms of action and you are only discussing one of them.
> Its multistage inhibition entails the process of selective binding to the interface between capsid subunits and such interaction determines the inhibition of capsid-mediated nuclear uptake of HIV-1 proviral DNA (by blocking nuclear import proteins binding to capsid), virus assembly and release (by interfering with Gag/Gag-Pol functioning, reducing production of CA subunits), and capsid core formation (by disrupting the rate of capsid subunit association, leading to irregularly formed capsids)
pitpatagain · 15h ago
This is incredibly misinformed, the drug has been specifically studied as prep, and this is in fact not at all what happens, despite your theories about the drug's mechanism of action. It does prevent infection.
tremon · 15h ago
If the virus doesn't replicate, does that also means it doesn't transfer from an infected person to their partners? If so, that would also fall under "provides protection against HIV infection" for me.
brookst · 15h ago
It’s an insightful and society-forward observation, but I do think a person taking the drug who found they were infected but not contagious might take issue with the “prevents infection” framing.
Assuming GP is correct, from other comments it sounds like that’s in question.
est31 · 13h ago
Initial infection and persistence are different things, and the reservoir for HIV builds up early on, but not immediately. There is definitely at least one reproductive cycle in between the first infected cells and the creation of a reservoir.
For those wondering, it's two injections a year compared to the daily PrEP pill.
cosmotic · 20h ago
There's also an existing option of a 6 times a year injection
inasio · 17h ago
Beyond efficacy, having a drug that only needs to be taken twice per year is a huge deal. Adherence is critical for treatments to succeed, and it's much easier to ensure that patients are on their meds twice per year. It's also much safer for vulnerable people, where getting caught with HIV medications (say daily pills) could be dangerous
octo888 · 18h ago
A twice-yearly injection with the same efficacy as daily PrEP is a fantastic development
thehappypm · 10h ago
Sidebar but HIV has led to some really amazing antiviral research. I really hope that this research will be helpful during the next pandemic. That’s a silver lining for a truly horrible disease.
Ey7NFZ3P0nzAe · 5h ago
Can't source but I've heard that the study of virus really only took off after HIV started, so most papers on viruses are actually about HIV. Could be wrong though
croemer · 13h ago
The drug's name sounds like "Yes to go", most certainly not a coincidence
smsm42 · 17h ago
That sounds great, but the "100%" part makes me worry. I don't know a lot of 100% effective medicines, there are always corner cases, and if they are claiming there aren't they are either exceptionally awesome, or lying. The experience teaches me liars are more common that exceptional awesomeness...
rendleflag · 17h ago
What's to prevent HIV from evolving past the protection? Strains of gonorrhea (a bacteria) has evolved to get around antibiotics. Won't that happen with HIV? Or is a virus not able to adapt?
jerojero · 17h ago
It depends on the drug but generally the principle is trying to target a part of the virus that is so fundamental to its structure that it simply cannot adapt to function without it.
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.
tonyhart7 · 17h ago
same like always, we develop a better antibiotics???
yieldcrv · 13h ago
the war on retroviruses is based on taking new approaches that aren't limited by this issue, while also slowing down existing infection long enough for your natural immune system to deal with what's there.
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
qgin · 14h ago
Yeztugo
Yes, (ready) to go
I would love to sit in on branding meetings for pharmaceuticals.
amadeusw · 13h ago
I appreciate your insight, the first association that came to my mind was a generic brand name on Amazon
throwawaylaptop · 12h ago
Should we mandate that all school children take this? Maybe make it a requirement for employment? I'm sure there's negative side effects, but all vaccines and drugs have that.
If we did, we could end a lot of suffering in a decade or two for many at risk people.
magicloop · 16h ago
In terms of difficulty was the HIV drug harder to develop than the COVID vaccine? If so, how much harder? The resolution of the AIDS epidemic, granted the logistics and targeting now needed, is such a brilliant milestone.
gschizas · 20h ago
I'm a little wary with "100% effective". Not even 99.9% effective?
pkulak · 20h ago
Not a great title, it would seem:
> provides HIV-negative individuals around 99% protection from contracting the devastating virus through sex
randcraw · 20h ago
Not a well written article in other ways too. What's the booster interval? What's the expected market coverage? How expensive is it, especially in poor countries where it's needed most? Are there challenges in transportation or storage that will limit its adoption? How does its efficacy as a preventative compare to its efficacy as a treatment (the reason it was approved in 2022)? Lots was left unsaid by this article.
You'll note also, the sole source for the article is Gilead (mentioned at the end), the drug manufacturer.
freeone3000 · 20h ago
These are better covered by Gilead’s actual press releases, of which this is a very poor summary.
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.)
> I truly believe that if any company can be morally good, Gilead qualifies.
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.
Do you know how much a liver transplant is? That was the alternative.
freeone3000 · 10h ago
They created a way to live with AIDS. They were the first. They did it in the 90s, where even working on this had significant stigma still. Friends are alive because of them.
ksherlock · 20h ago
Wikipedia says:
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,"
It's curious that the article (and wikipedia) specifically refer to sexual acquisition.
GuB-42 · 18h ago
Maybe the other routes simply weren't tested for. Sex is how most people get HIV, so it makes sense to start from here. The second most common is by sharing needles, usually by drug addicts, and I can't think of an ethical way of doing a trial in such conditions. The rest is mother-child transmission, which is irrelevant as the drug is not intended for fetuses, and the odd accident which is probably too uncommon to make meaningful statistics.
aerostable_slug · 19h ago
Wouldn't sexually active people who have sex with men be the primary market? It makes sense this would be the focus of the drug's development.
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 · 19h ago
Prep has been studied for IV drug users. It works, enough that it is recommended, but is much less effective. IV drug use is a massively more efficient transmission route than any type of sexual contact.
42772827 · 18h ago
>IV drug use is a massively more efficient transmission route than any type of sexual contact.
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 · 18h ago
Asking here instead of searching, for conversational purposes:
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 · 18h ago
It's true that it's less likely, but calling it "unlikely" is grossly irresponsible. Yes, the chance is only 1-2%, but that's per vaginal sexual encounter. (And it's also "only" 20% for anal.)
That doesn't match what the top study says: 1.4% for anal and 0.08% for vaginal.
> 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 · 12h ago
Ah, you're right. I pulled a totally unrelated statistic. Complete nonsense to say that it's unlikely for vaginal sex.
badlibrarian · 10h ago
In the fog of the day, you can understand why 1 transmission per 1,250 occurrences qualified as unlikely. Female prostitutes were self-reporting that they didn't use condoms and weren't showing symptoms. Meanwhile the disease decimated the gay male population which is why it was called GRID ("Gay-Related Immune Deficiency"). It was a complicated and horrible time and the data really wasn't there.
kstrauser · 17h ago
Yeah, agreed. That was the takeaway 3 decades ago, and I only bring it up no out of curiosity of how erroneous that turned out to be. I’d hope no one would describe it that way today.
What is the target audience for these bi-anual shots? Only populations at high risk or are we supposed to start vaccinating everyone that is sexually active?
Btw, nothing on the article about potential side effects.
42772827 · 17h ago
>What is the target audience for these bi-annual shots?
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/
That would be up to individuals or health departments, who decide what risk is high enough. The risk for non-promiscuous people in 'western' countries is so low, that I don't see any country giving this to everybody.
This is not a vaccine, BTW, and it needs to be given every 6 months.
yieldcrv · 13h ago
Unless low-risk people are getting shots twice a year too, I don't see this as reaching the goals that are as monumental as the article and Gilead suggests.
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.
thighbaugh · 17h ago
Given that sugar pills still have a curative effect on some portion of patients and that 100% effective sounds pretty unscientific as a figure (nothing is 100% hence the need to use statistical confidence). I pray that I am wrong in smelling something being rotten in this lot but only time will tell.
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).
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).
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.
There's no good reason a liver transplant should cost 300k, so yours is a false comparison.
Pharma companies are gamblers. They gamble on the cost of R&D, the market size for the drug, the amount they will be able to charge. The higher the expected value of their profits, the wider variety of drugs look like attractive prospects financially.
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.
Switzerland is one of the few countries where getting paid more in the US for the same job would generally not be an "as usual" :) The large majority of equivalent jobs gets paid more in Switzerland, including office ones. The ones that don't are the outliers (which are of course greatly overrepresented here on HN).
This is IME, so feel free to correct me if I'm wrong.
https://www.healthline.com/health-news/heres-how-much-more-o...
- *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...
Surely that's something that would be easier to get bipartisan support for, somewhat avoiding the "socialism vs capitalism" chasm between the parties that prevents meaningful healthcare reform.
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.
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...
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.
No comments yet
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.
Part of the reason the US has a higher GDP is because we work longer hours and take less vacation. "You work harder, therefore you should shoulder more" hardly seems fair.
Europe makes fun of us for our defense spending yet demands protection, makes fun of us for working long hours yet says we should shoulder more, makes fun of us for overspending on health care yet charges us 10X as much for the drugs they manufacture: https://www.healthline.com/health-news/heres-how-much-more-o...
I just can't shake the feeling that Europeans see Americans as suckers.
> we work longer hours and take less vacation.
Yes, but people working longer hours doesn't necessarily translate to more output, especially when quality is taken into account.
Anecdotally, from what I've heard from people working in international companies, the American work culture doesn't seem to be very efficient when looking at the end result. The studies of 32 hour work weeks seem to indicate similar findings, though like the anecdotes, should be taken with a grain of salt of course. But I truly believe that in most cases, a developer who works 10 hours a day will not produce more than one who works 6 hours a day, at least after a couple of days.
>Europe makes fun of us for our defense spending yet demands protection
You do realise that until very recently, America has gained an absurd amount of soft power through this defence spending, right? And was able to convert this soft power into a lot of GDP through indirect subsidies of its international companies? Just because the current administration has squandered this advantage, doesn't mean you did not get out more than you paid for the last couple of decades.
>I just can't shake the feeling that Europeans see Americans as suckers.
I agree with you on that point,but not for the reasons you might think. I see the "temporarily embarrassed millionaire" phenomenon, people constantly against their self-interest and the like, and and it's hard not to. I have relatives in the US, and I still feel sympathy for your people.
But it's getting harder and harder to not see you as suckers when you look at the tariffs or the cuts to welfare, science and education, all while the rich get massive tax cuts. And all is being done in the name of "draining the swamp", by a billionaire who is incredibly well-connected with 90% of the corrupt elite he publicly opposes.
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.
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.
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.
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?
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.
1 - Premium
2 - Co-Pay
3 - Deductible
4 - Co-Insurance
5 - Balance Billing -- you dont learn the full cost until weeks/months later
6 - Non-covered items -- you dont learn the full cost until weeks/months later
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.
Well, fuck that. I'm already paying $24K annually for my health care that covers about half of anything short of a catastrophe.
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.
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.
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.)
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.
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...
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!
"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.
people magically get more vigilant is as leakly as virus magically goes away on its own.
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?
[0] https://en.wikipedia.org/wiki/Risk_compensation
>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_...
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.
> The medication works in two ways: First, it interrupts viral replication by preventing HIV from reaching the nucleus of an infected cell, which then blocks reproduction.
> The second mechanism is for cases in which integration of the HIV genome has already occurred. In this instance, lenacapavir interferes with production of viral progeny
In other words, it has multiple mechanisms of action and you are only discussing one of them.
Another source is https://pmc.ncbi.nlm.nih.gov/articles/PMC10705863/ (my emphasis):
> Its multistage inhibition entails the process of selective binding to the interface between capsid subunits and such interaction determines the inhibition of capsid-mediated nuclear uptake of HIV-1 proviral DNA (by blocking nuclear import proteins binding to capsid), virus assembly and release (by interfering with Gag/Gag-Pol functioning, reducing production of CA subunits), and capsid core formation (by disrupting the rate of capsid subunit association, leading to irregularly formed capsids)
Assuming GP is correct, from other comments it sounds like that’s in question.
https://pmc.ncbi.nlm.nih.gov/articles/PMC4593515/
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
I would love to sit in on branding meetings for pharmaceuticals.
If we did, we could end a lot of suffering in a decade or two for many at risk people.
> provides HIV-negative individuals around 99% protection from contracting the devastating virus through sex
You'll note also, the sole source for the article is Gilead (mentioned at the end), the drug manufacturer.
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...
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
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.
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.
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.
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?
https://stanfordhealthcare.org/medical-conditions/sexual-and...
https://pmc.ncbi.nlm.nih.gov/articles/PMC3412216/
> 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).
[0] https://stanfordhealthcare.org/medical-conditions/sexual-and...
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/
[0]https://pmc.ncbi.nlm.nih.gov/articles/PMC4430426/
This is not a vaccine, BTW, and it needs to be given every 6 months.
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.