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?
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.:
> 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).
But if they are offering royalty-free production to generic manufacturers, why wouldn't insurance companies simply insist on using the cheaper generic?
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.
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.
> 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.)
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.
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.
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.
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.
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.
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.
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.
> 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)
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:
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.
This is great information and obviously new to me. I had thought it only interfered with cap formation but it appears to also interfere with capsid penetration of the nucleus and therefore integration of the virus with the host cell genome.
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.
How, exactly, does the “specifically studied as prep” process determine whether a person *who is taking a very long-active antiviral medication” acquired HIV?
It gives no details whatsoever about how testing was performed except to mention that both rapid and central laboratory tests were used. It does not discuss whether the study medication could interfere with testing. It does not even say whether the tests looked for antibodies, RNA or something else. The actual study protocol is in the paywalled supplement information.
I’m not saying the studies are wrong. But I would be a lot more impressed if the studies actually discussed the issue.
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.
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.
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.
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
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...
Readit News
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).
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.
But $84k seems a little pricey. Imagine paying that out of pocket.
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.
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.
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.
> 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)
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.
So obviously I retract everything I said above .
Here’s one of the papers:
https://en.iacld.com/UpFiles/Documents/1e4ad0d2-4a73-4365-9b...
It gives no details whatsoever about how testing was performed except to mention that both rapid and central laboratory tests were used. It does not discuss whether the study medication could interfere with testing. It does not even say whether the tests looked for antibodies, RNA or something else. The actual study protocol is in the paywalled supplement information.
I’m not saying the studies are wrong. But I would be a lot more impressed if the studies actually discussed the issue.
Assuming GP is correct, from other comments it sounds like that’s in question.
https://pmc.ncbi.nlm.nih.gov/articles/PMC4593515/