One other very cool thing here is that this new treatment represents a whole new family of drugs (very sophisticated at that, per Derek Lowe's assessment). I thought back in the late 2010s with integrase inhibitors (e.g. dolutegravir), there was a real chance they could achieve the 90-95% reduction targets in new cases, and hopefully this new drug makes that even more feasible.
There's always the risk of losing previously effective drugs due to resistance, so the value of redundancy cannot be overstated
Not my field so please bear with me. Before watching the video
the notion of interfering with the capsid as a mechanism for stopping the virus made sense.
However, what I still don't have a handle on is how does lenacapavir act so long that it only needs to be administered every six months?
From the explanation lenacapavir works on the capsid directly, it's not acting on the immune system by training the body's defences as with a traditional vaccine. Surely this molecule can't just hang around for six months without being gobbled up by the liver or such.
It's got so many fluorines running around that intuitively as an amateur chemist I would expect it to have an extraordinarily long half life in the human body, especially so if it's administered as a depot injection in something with a large molecular weight. It takes your body a long time to chew through the inactive components in a depot injection.
Yeah, I also noted the fluorines (and Lowe's comment), and I know they're used to prolong action such as with, say, fluoxetine with its three fluorines but six months seems extremely long. I'd have thought it'd have been flushed out long before that. Presumably, it must bind to lipids, fats etc.
Anyway, whatever, it's clearly a brilliant bit of chem eng.
> Surely this molecule can't just hang around for six months without being gobbled up by the liver or such.
It can! The fluorines likely protect the metabolic target. At that point you're relying on excretion of unchanged drug through the kidneys or liver (which excrete into bile, and then eliminated in feces).
Google tells me the half-life of the subcutaneous administration is 2 to 3 months, so twice yearly injections makes sense.
I would have thought that too but at one point I had clients taking a bone loss drug called Alendronate. Looking up the drug I was shocked to see that it has a 10 year half life in bone tissue. So yes some drugs once taken will stay in certain tissues for a very long time.
"I was shocked to see that it has a 10 year half life in bone tissue."
Well so am I. One of the great things about HN is the sheer amount of stuff I learn from others who post here. Alendronate is yet another instance. :-)
As Alendronate, Alendronic acid, is not a drug I'm familiar with I've just looked it and its structure up on Wiki to get a rough idea what it's about.
I'm not doubting Alendronic acid's 10 year half life in bone tissue but I'm now curious how that comes about. It has five hydroxy groups which I'd have thought would have made it highly soluble in water. And —OH groups tend to be reactive.
As I said, biochemistry isn't my field but I'm now intrigued about how it actually works. No doubt the phosphorus bonds to or goes into strengthening bones but why that doesn't happen immediately has me stumped. So experts I need your help.
Clearly, many chemicals can and do survive in tissue for years, PFAS being an example but we don't think of them being highly reactive either. Obvious examples of chemicals that aren't eliminated by the body that everyone is familiar with are tattoo dyes. No doubt a bad example as they don't seem to be biologically active and remain more by mechanical adhesion than by any other means.
The issue I don't have a good handle on is how biologically active drugs can remain unchanged for so long before being taken up and used by the body. Perhaps they're stored as intermediate metabolites or similar.
PFAS only describe one part of the overall molecule. It doesn't necessarily tells if the rest of the structure is toxic or not. It's like saying "I though canine were dangerous?" (yes for big cats, no so much for your average French bulldog).
It's somewhat unclear, but given that they've been found in every piece of human tissue tested for it, I'd say at the very least it kills slower than HIV. Of course there are many different kinds of PFAS, some might be worse than others.
Most vaccines have had some toxic component in them particularly historicaly. If you look up different vaccine types over the past 50 years you'll see often ingredients are removed or replaced because of it. The general wisdom is that it's either small enough quantities that you'd have less negatives from the toxicity than you have from being able to prevent the disease at a population level.
This is a paper describing the pharmacokinetics (the rates of various phases of entering the blood and clearing out of the body) for various formulations of the drug, and their hypotheses for why this might be the case:
tl;dr: the molecule is poorly soluble in water, so by suspending a bunch of microparticles and injecting them subcutaneously, the drug very slowly dissolves over time, and it’s very potent, so only a little bit is necessary to do its job.
It does in fact prevent infection you have misunderstood.
It very clearly prevents infection incredibly well, proof of that in the real world is exactly why there is excitement over this drug.
It also sounds as though you misunderstood the mechanism, it interferes in both an early and a late step in the viral process, there no theoretical reason to describe it as "not interfering with infection".
From what I read, it interferes with capsid formation. Since HIV is a retrovirus, by the time capsid formation is happening it has already integrated itself with the host cell’s DNA.
That implies that as long as the drug is present, the virus won’t be able to replicate, however as soon as the drug is no longer present the virus will start replicating. Because the cell has been infected.
Of course, the illness cannot get worse without the virus first infecting a cell, and then replicating in that cell to infect other cells in the body, and then potentially infecting other hosts; that is how a virus works, right?
Now, if replication is stopped, AND the body is able to destroy the first infected cell, then the patient is cured, but otherwise?
I guess that even if the body's immune system cannot get rid of that "patient cell zero", it is quite possible that a 6 month period is enough for the cell to die from the virus.
I do not have any medical training though, so please correct me if I am wrong.
>There's always the risk of losing previously effective drugs due to resistance, so the value of redundancy cannot be overstated
Redundancy in HIV drugs is extremely important and significantly more resources should be applied to such drugs, as well as to treatment regimens and vaccines that can significantly reduce HIV infection and the horrible effects of AIDS.
In fact, we've made enormous advances over the past 35+ years. My (late) sister's (late) husband was a hemophiliac and, like most American hemophiliacs[0], was infected with HIV because big pharma refused to test the blood products[1] they were selling to hemophiliacs, even though they knew there was a significant risk in doing so.
In any case, my sister took care of her husband for nearly 15 years, until he finally died a slow, painful death in 1996. My sister was also HIV+ and didn't wish to suffer the way her husband had, especially since there was no one to care for her the way she cared for him. And so, over Memorial Day weekend, 1996, my sister took her own life rather than die a slow, painful death.
The irony, of course, was that the first protease inhibitors were approved by the FDA five or six months later. Had she waited, she might well be alive today. And more's the pity.
As such, I strongly believe in research to prevent, treat and cure HIV/AIDS, and heartily agree that we need more good drugs and treatments.
However, the value of anything can be overstated, including redundancy in HIV drugs.
"Without significant redundancy in HIV drugs, all life in the universe will be extinguished."
"Without significant redundancy in HIV drugs, our sun will explode in 2043."
"Without significant redundancy in HIV drugs, the oceans will boil, then evaporate in the next six weeks."
I could go on, but I presume you get the idea.
Hyperbole can be a short-term motivator, but we need to continue over the long term to stop HIV/AIDS. So, please do advocate for more research/drugs/treatments, but please don't use such language in doing so -- it cheapens the argument and potentially reduces the resources available for the efforts you clearly want.
Feel free to disagree, but doing so will give you terminal cancer.[2]
> Hyperbole can be a short-term motivator, but we need to continue over the long term to stop HIV/AIDS.
I am expecting the findings of this trial to be regurgitated by the general population who refer to the science community. “THEY cured AIDS” will be declared without the nuance of “well, new infections are prevented with a biannual depot injection …”
> Redundancy in HIV drugs is extremely important and significantly more resources should be applied to such drugs
Does HIV prevention research get more resources than curing cancer? I'm looking through the NIH website and asking Claude and so far the evidence I've seen is leading me to believe that's true, but I could be mistaken.
>Does HIV prevention research get more resources than curing cancer? I'm looking through the NIH website and asking Claude and so far the evidence I've seen is leading me to believe that's true, but I could be mistaken.
I don't know. Does it matter? If you think it does, why?
Note that I wasn't advocating for resources to be taken away from research on treatment/cures for other diseases.
That said, more resources should be applied to curing cancers and other deadly diseases as well.
I wonder how much this will cost? A drug you take 2 times a year could be much cheaper than one you take 365 times a year, and that's a big deal.
The existing daily pill is really expensive. Australia knew that PrEP would practically eliminate HIV transmission. Even so, the decision to pay for it took years and was fiercely contested. That was before COVID, and people are more willing to pay for public health today. But cheap PReP would make a big difference in the poor countries where HIV prevention really matters.
The shot will likely be exorbitant in the USA. Gilead charged almost $2k/month for Truvada (list price, of course) and Descovy is the same. Generic Truvada is like $30/month now, so the price was never about the cost to manufacture. Obviously Gilead is developing these new drugs/shots for when Descovy's patent expires.
They rely on the government mandating that health insurance companies cover the shots. This drives up the price.
The price is rarely ever about the manufacturing cost.
"A new study in 2020 estimated that the median cost of getting a new drug into the market was $985 million, and the average cost was $1.3 billion, which was much lower compared to previous studies, which have placed the average cost of drug development as $2.8 billion.[4]"
It should be pointed out that looking at the average cost of developing a drug is misleading, since one has to include the cost of all the drugs that failed to make it to market. One also has to include the money spent by small companies that failed and were not bought out, not just the money the big companies spend buying the successful ones.
This is critical, and exactly the sort of thing someone will gloss over, intentionally or not. The numerator is the total cost of developing ALL the drugs, even (especially) the failed ones, but the denominator is only those drugs that are successful.
On the contrary, often pharma proponents will gloss over the fact that most “failures” are discovered and canned at a small fraction of the investment of getting a drug to market (when it’s obvious it won’t do what you need or has other challenges).
Actually not in the contrary - you are right. It’s just that the failures often cost a small fraction. They don’t get to 95% testing and approval before “nope, not even close”.
No, that's not quite accurate - the phases are effectively additive.
37% fail in Phase 1. Of those that make it through, 69% of those fail in Phase 2, and of those, 42% fail in Phase 3.
So, of 1,000 possibles, you have 630 make it through Phase 1, and 195 that make it through phase 2, i.e. 80.5% of your drug candidates didn't even make it to Phase 3, that "most expensive phase".
A more accurate phrasing would be that 42% of the drugs that made it through Phase 2 fail to make it through Phase 3.
Supposing the cost ramps up exponentially at each phase, e.g. it costs $10 million to get to Phase 1, $100 million to get to Phase 2, and $1 billion to get to Phase 3, then we see the total expenditure for 1000 possible drugs as:
$ 3.7 billion for Phase 1 failures (370 drugs)
$ 43.5 billion for Phase 2 failures (435 drugs)
$ 82 billion for Phase 3 failures ( 82 drugs)
$113 billion for Phase 3 successes (113 drugs)
This sums to a little over $242 billion spent against 113 successful drugs, or about $2.14 billion per successful drug, or more generally, accounting for failed drugs, the full cost of a successful drug is a little more than twice what was directly spent on its development.
Certainly I do not mean to imply that Phase 1 and Phase 2 failures are cost-free. But it is challenging to measure. As seen elsewhere in this thread, Gilead essentially included the acquisition of another company who had a whole retinue of drugs and product lines as "R&D" for Truvada, I believe. That is creative accounting that would not pass an audit or SEC filing, which is why Gilead only counts it as an R&D cost in their press releases...
It certainly should count; that company didn't get delivered for nothing by the Drug Discovery Fairy. And even more: the companies that didn't get bought by Gilead should also count, since the funders of all those small companies could not tell ahead of time which would succeed enough to be bought out.
No, it really shouldn't. If I acquire a drug company that has, say, 100 patents on a suite of drugs for $1B (just using nice round numbers), I don't get to say "I spent $1B on "R&D" for 1 drug" as a sunk cost.
R&D is a sunk cost. Presumably acquiring an active company with a portfolio is an investment.
Published estimates of trial costs from a 2011 systematic review ranged over an OOM.[1]
A 2017 report focused on 7 top-20 companies and 726 studies from 2010-2015 found " median cost of conducting a study from protocol approval to final clinical trial report was US$3.4 million for phase I trials involving patients, $8.6 million for phase II trials and $21.4 million for phase III trials". [2] These are not all that far off from another 2016 study on cost drivers of pharma clinical trials in the US using means and breaking down costs by therapeutic area. [3]
Plugging the first study's numbers into your 1000-drug profile, we'd have:
$ 1.3 billion for Phase 1 failures (370 drugs)
$ 3.7 billion for Phase 2 failures (435 drugs)
$ 1.8 billion for Phase 3 failures ( 82 drugs)
$ 2.4 billion for Phase 3 successes (113 drugs)
That sums to $9.2 billion spent against 113 successful drugs, or about $80 million per successful drug. This implies the full cost of a successful drug is almost 4x what was spend on its development.
One limit here is we're working with medians, not means, and I wouldn't be surprised if this is an underestimate of clinical trial costs.
Roche has had pretty stable net income (profit) of $9.2-$15.2B/year from 2011-2023 against revenue from $49.9-$72B/year in the same time period. Using this estimate, ignoring inflation, if they ran 1,000 clinical trials per year it would account for a maximum of about 18% of their costs and they'd get 113 new drugs out of it annually.
Obviously that is not what's happening: there are an average of 53 FDA new drug approvals per year across the entire industry. If Roche was the only pharma company running clinical trials, the total cost of those trials would be more like $4B, so a max of about 10% of their annual costs. In reality this estimate makes it seem like it must be substantially lower.
The Congressional Budget Office[4] says total pharma R&D spending in 2019 was $83 billion. With 53 new drug approvals per year on average, that implies about an average cost of about $600 million per drug in R&D spending, compared with the $80 million estimate obtained above.
So this makes it sound like running clinical trials account for only about 10% of total R&D spending. Given that Roche's costs alone look to be in the tens of billions per year, as compared to $83B or so annually for R&D across the industry, it also looks like R&D is only a part of the story on cost drivers for pharma companies. Google is not being helpful on this question (almost all the conversation is on R&D cost, it seems), but my guess is it's costs of manufacture, legal, sales, etc.
> it also looks like R&D is only a part of the story on cost drivers for pharma companies ... but my guess is it's costs of manufacture, legal, sales, etc.
Marketing. At least 7 of the top 10 pharma companies globally have marketing as a multiple of R&D for their spending (sometimes up to 7x). IIRC, at the other 3, it still exceeds R&D, less egregiously.
The big issue with "Marketing" spend is that though these numbers are global, there are only two countries in the world where you can advertise prescription medicines to consumers: the US, and New Zealand (and the latter, if I recall, is trying to phase it out, and only allowed it after being bullied by the US on a Trade Agreement).
So you end up with "US Marketing spend at many pharmaceutical companies grossly outpaces their global R&D spend" (and while a not insignificant portion of R&D happens in the US, most of those companies also have a notable R&D investment in Europe).
Marketing wouldn't go to zero without that, of course, but it'd be a huge sea change.
> One also has to include the money spent by small companies that failed and were not bought out, not just the money the big companies spend buying the successful ones.
If you're looking at the total amount spent by "the economy" (drug development costs X% of GDP), sure. If you're looking at "why are drug prices so high", it probably doesn't make sense to to include costs funded from other places (which in this example I assume would be research grants ie taxes, and venture capital funds).
For the private parts of development, the costs are absolutely priced in. A large drug company needs to amortize the cost of all development attempts, not just the successful ones. Private investments into smaller firms price in a very large chance of failure, so the cost of capital is quite high.
That's not quite right. A drug company with a new product will charge whatever the market will bear. What the costs do is control the scope of the industry: if profits are high, the industry expands to try more kinds of drugs, stopping when the attempts on the margin are just profitable enough (on average). If profits are not expected to be adequate, the industry contracts.
Perhaps you prefer: A company must think it's likely that they'll have a good return on all development costs, not just the costs of drugs that happen to be successful, to continue to invest.
> if profits are high, the industry expands to try more kinds of drugs, stopping when the attempts on the margin are just profitable enough (on average).
Of course, something like pharmaceutical products, with exclusive sales of specific products, few sellers, strategic conduct relative to other industries (insurers), and heavy regulatory influence is not guaranteed to converge to normal profit.
The problem with this argument is it assumes the cost of a failure is the same as the cost of success, which it cannot be: the successful drug has to go through more rounds of testing and approvals than a failure.
In reality many failures are early or first round failures. Not free but a small fraction of the price of getting to market.
So to you example a 90% failure rate may only require a 2x or 3x return on your successes to “break even”.
"They found that the probability of success was 63% in Phase I trials, 31% in Phase II trials, 58% in Phase III trials and 85% during the regulatory review process"
42% failure rates in phase 3 is enormously high. By then you've pretty much spent 90%+ of all the cost of getting a drug approved.
But it's 42% of 19%. So out of 1,000 drugs, you're looking at 805 being ruled out before you even get to that "most expensive phase", which is my point. At Phase 3, you're looking at 113 succeeding, so you're "only" eating the really expensive[1] costs of Phase 3 for 82[2] of 1,000 attempts.
[1] Which isn't to say there's zero cost for Phase 1 or Phase 2, but it's a lot lot less than Phase 3 trials.
[2] 1,000 drugs, 63%, 630 of which make it through Phase 1. In Phase 2, 195 drugs, 31% of 630 succeed and make it through to Phase 3, and then 82 drugs (58% of 195) make it to regulatory approval.
> "A new study in 2020 estimated that the median cost of getting a new drug into the market was $985 million, and the average cost was $1.3 billion, which was much lower compared to previous studies, which have placed the average cost of drug development as $2.8 billion.[4]"
PrEP repurposed Truvada, an existing blockbuster drug that had already reaped immense profit for Gilead for use in HIV treatment by the time the trials for PrEP began. The trials for PrEP were funded by the government, not Gilead. Gilead, however, got to retain all profits earned from PrEP.
Did Gilead fund the R&D? There's a lot more to developing a new drug than just trials (though I think Gilead should have foot the bill for the trials too).
I don’t know if it’s the case here, but very, very, very often in biotech you’ve got the primary foundational research happening at university labs funded by grants, and it’s the productionization of the research (and then clinical trials, etc) that are what the biotech companies are doing. I’m not sure where that shifts the “who deserves what” conversation, but without university research labs, there’s no pharma industry.
If the university owned the IP, then its value should have been reflected in what was bid for it.
If the knowledge was not restricted by IP law, then any drug company could use it, and compete for new drugs based on it. As such, it would not provide any of them with a competitive advantage, and so would not be reflected in what they could charge.
What universities typically produce is not a chemical that can serve as an actual drug, but is only a starting point for a long and expensive process of producing such a chemical. And then, it's often found that the target of the class of potential drugs isn't actually a good one. One can't determine that until drug candidates are available to test on real patients.
> What universities typically produce is not a chemical that can serve as an actual drug, but is only a starting point for a long and expensive process of producing such a chemical
Remember you need to include all the failed attempts at finding useful things at university labs to see how much governments spend on research (just like you did failed pharma attempts), and if you add that up you see governments actually contribute a massive part of the cost to bring medicines to market.
What they produce is necessary to even begin the work pharma does, currently it is basically a gift from the people to the pharma industry.
"without university research labs, there’s no pharma industry." - I think you have it exactly backwards: Without the pharma industry, there's no medicine. Good research goes nowhere if you can't bring it to market.
The pharma industry COULD do their own foundational research, but the university system cannot bring a drug to market.
> The pharma industry COULD do their own foundational research
Citation neeeded - have they ever done so? Would the shareholders accept it? Would they be able to manage borderline autistic PHD types detached from reality, and would these scientists want to work there?
PhD types doesn't mean they make foundational research.
> They are numerous, smart, very cheap, and work very hard.
Yeah, this is a good reason to hire such people, but they generally don't do foundational research work at companies, and if they do it is extremely narrow.
Just like government work the problem is the environment, Governments hires management and planning types just like companies do, but that doesn't mean they can scale up like a company can. Same with foundational research, private companies aren't a good place to do that.
It's difficult to overstate just how menial, fiddly, difficult, risky, time consuming and unclearly profitable foundational biomedical research is. A research project could easily take 4-5 years, have a 5% likelihood of success, and have no clear monetizability, yet end up being a groundbreaking foundational result and necessary to investigate.
In other fields, either there's some tangible hope of profit down the road, or at least you can attract talent and prestige. Not so much here.
The direct role that university research plays in drug development is overstated. The majority of cost and difficulty in pharma is _drug development_ not _drug discovery_. Pharma can do the discovery and the development, academics can only do the development. Absent academia, we'd have less drugs. Absent pharma we'd have no drugs.
Academics focus on drug discovery because it's better aligned with academic incentives and timelines (see this commentary for a brief description [0]). Drug development costs (including clinical trials, extensive and repeated med chem, etc) are borne mostly by drug companies.
Fair data on this is hard to come by because the two main sources have clear conflicts of interest (academics and pharma industry publications). One study Derek covered before (data from 1995-2007) shows only 24% of drug scaffolds were first found at a university and transferred to a biotech or pharma for development [1]. You can break this down further to highlight any story you want to support ('university ID'd drugs more innovative' vs. 'pharma ID'd drugs help more people') but they key point is that combining all the US research leads to only 24% of drug scaffolds that make it to market.
I think everyone acknowledges that outside of finding the scaffolds and the basic biology, pharma is paying the vast majority of clinical trial costs. [2] gives a figure of total NIH funding of clinical trials at 10% of overall (e.g. pharma covers 90%).
I think an argument could be made that the NIH training grants (which pay grad students in the biomedical sciences) subsidize the work force substantially, and might have a higher impact than direct research grants. I couldn't find quantitative data on this with a quick search, but I think this is often overlooked in the discussion.
Finally, a less quantitative pieces make me think the impact of the NIH/government funding is overstated even given the above numbers. In my own field (microbiome), academic research has been almost inimical to the production of quality drugs. For every disease there exists a paper suggesting that a certain gut microbe changes the likelihood/severity/X about that disease. Academic labs have incentives to publish significant results fast, and in the microbiome this has led to a) abysmal signal to noise ratio with very high likelihood of failure to replicate, and b) an epistemic closure about what types of microbiome data matter and how they should be pursued as drugs that is totally divorced from the reality of how drugs are developed. Much of the knowledge base is polluted by low-quality research that has been done for the purpose of publishing. While the NIH spends ~40 billion a year on external research grants [3], I think you have to heavily discount this for the amount of just pure "grad student needs to graduate gotta publish" material that gets produced.
i've always viewed big pharma as like pre-internet record labels. they pick up talent (that often comes from bohemia aka government funded research), vet it, run the trials and put up the money, do the engineering to deliver it at scale and then market it.
A significant portion of the cost is the drug trials. Excedrin Extra Strength and Excedrin Migraine have identical formulations, but IIRC Bayer spent $300m on FDA approval for migraine treatment, which is why the migraine variant continues to be more expensive.
>
A significant portion of the cost is the drug trials. Excedrin Extra Strength and Excedrin Migraine have identical formulations, but IIRC Bayer spent $300m on FDA approval for migraine treatment, which is why the migraine variant continues to be more expensive.
Your analogy would only be relevant if the US government paid $300M for the FDA approval and Bayer got to pocket 100% of the markup.
A 2022 study invalidated the common argument as is for high medication costs that research and development investments are reflected in and necessitate the treatment costs, finding no correlation for investments in drugs (for cases where transparency was sufficient) and their costs.[20][21]
The Wikipedia editor was a bit naive to think such a basic study could invalidate that whole claim. They measured the correlation between the list price, adjusted for use amount, and development cost. As far as I can tell they didn't take into account number of customers each drug would have, how long the drug would stay on the market before profits are cannibalized by competitors (see e.g. Wegovy), and definitely not the cost of failed drug development.
Same with software. I saw IntelliJ costs $250/year but it costs almost nothing to send that file (it's like maybe 1 GB max, cents). You can get it from generics manufacturer on TPB but updates are not as frequent.
1. Pharmaceuticals actually don't do all their own research. Universities find the drugs and what they can treat, pharmaceuticals research the product viability. They make medicinal products, they're not research labs
2. The research is often majority funded by the government, i.e. your taxpayer dollars. So the costs are often socialized, but of course the revenue is not.
IntelliJ actually develops they're stuff, they don't just take existing code, test it a bit, and then make a product. And IntelliJ is a truly private company, pharmaceuticals are not because they get huge sums of money from the gov.
I'm no fan of pharma industry but there's an unfounded and troubling assumption embedded in this comment: that any drug price over cost-to-manufacture can only be extortion. How do people recoup R&D costs (which are the vast majority of costs in getting a new drug onto the market)?
The government funds a lot of early stage preclinical research. These are the inexpensive stages of the pipeline.
As soon as you move into humans you can add another 2 or 3 zeros to your burn rate.
It is not politically feasible for the public sector to fund later stages. The numbers are just too big. Just think of the campaign ads that would run around $200M late stage failure funded by the government.
The reason why mega giant pharma companies exist is because they make enough money and are capitalized enough to withstand multiple $100M failures without going belly up.
The public gets access to a life-saving drug that otherwise would not exist, which is exactly what the government is paying for. You can reasonably argue they they should get more, but arguing that they should get some ROI is moot; they're already getting a tremendous ROI
The public gets the privilege to be price gouged for stuff their taxes paid for. Doesn't sound like a good deal. Many will not have access at higher costs. Price gouging restricts access.
Are you saying the public would prefer that the drug not exist over the drug being expensive? If not, the public is getting a return. Like I said, it is reasonable to argue that the public deserves more return, ie. that it's a bad deal. But the argument that it's paid for by taxes and therefore should provide value to the public falls short of disagreeing with the status quo.
I'm saying it may as well not exist for people who can't afford it. You might say it's worse than not existing when it does exist but they can't have it because you would rather people die than receive treatment, due to your weird ideas about people making money and how justified that is.
Your bend over backwards justification of greed over human life is rather insane.
It clearly seems not to be the case that this treatment "might as well not exist" for people who can't afford it, in that it has been administered to many people in Sub-Saharan Africa, and likely will continue to be.
Further: omit things like your last sentence from your comments; they hurt your case.
> Further: omit things like your last sentence from your comments; they hurt your case.
It hurts people more to deny them medical care, and that is what makes it so enraging, I would say reasonably so. Becoming angry at such absurdity is a reasonable response. I toned it down from something much harsher. It is a truly deranged position to advocate for denying access to health care breakthroughs, and then act like that's doing people favors, calling it expanding access when you want to deny it.
It makes little sense to me to advocate an explicitly inhumane action, then say I'm doing an ad hominem when I call it what it is. What do you call an opposing view which happens to be ad hominem to humanity in general? Misanthropic, I guess. Your sibling comment says hey now, I didn't say any of that, after having said all of that.
That's why people here argue in a passive aggressive fashion and advocate violence indirectly, like violence through economics or violence by withholding medical care or necessary services to undesirables. It doesn't read on the surface as uncivil, while still wanting others to suffer.
I agree about that phenomenon and it doesn't change anything about you shooting yourself in the foot by personally attacking people when making your case. Please stop.
I don't understand the point of lying about me when all of the evidence is directly above, six sentences in total length, and abundantly clear. That leaves me with the conclusion that, no, indeed, three times was not enough.
>You can reasonably argue they they should get more
>Like I said, it is reasonable to argue that the public deserves more return
>it is reasonable to argue that people should receive more benefit for their tax money
That brings us to six. Can I just add that I think a reasonable argument might be made that the public is entitled to a greater benefit from their contribution to drug research? Or is it supposed to be 77 times 7 times?
The word was used in the construction 'I don't think it makes sense that you would be lying, therefore I must conclude that I haven't gotten through to you', to justify my repetition.
It certainly has gone off the rails, but I am entitled to defend myself at least as much as you are entitled to tell me to stop. I haven't done anything wrong. I am finished now though
I'm not sure how many times I'm expected to say that it is reasonable to argue that people should receive more benefit for their tax money before you stop accusing me of disagreeing with that. Is it three?
Pardon the snark, but come on. Before you get to the point of throwing insults, take a moment and determine whether I've actually argued for the positions that you believe would make me weird and/or insane. And then don't do it regardless, but definitely don't do it if I've only ever said a very specific thing very precisely and very explicitly.
If the R&D cost (including amortised failures and whatever) for some hypothetical drug is $1B and the manufacturing cost is $100M for 100M doses. The drug should cost about $11 + a reasonable markup in a fully private system.
If the R&D costs are fully funded by taxpayers, it should cost $1 + a reasonable markup.
The public doesn't "get" anything if it still costs $11 (+markup) and a company is allowed to take a 1000% profit margin because they're only risking the $100M for the manufacturing.
There is a limited amount of money we can spend on medicine. Every overpriced life-saving treatment kills someone who is in turn denied resources for another life saving treatment.
The outcome for taxpayer ROI should be about the benefit to the public at large regardless of who commercialized it. Commercialization should eventually lead to better and cheaper version of the technology, which increases benefit to the public.
Of course, the people who worked to commercialize it deserve pay for their work, so the question is exactly how much.
I think it's perfectly fine to assume that it's a form of extortion to profit from life-saving products, which is why some people agree that pharmaceuticals shouldn't be a for-profit industry at all.
> the vast majority of costs in getting a new drug onto the market
Debatable.
> according to these firms' annual reports, 16 percent of revenues was taken as profit, and • 31 percent went for marketing and administration. That's nearly three times as much as their R&D spending.
Maybe, but even people with chronic conditions might not go to doctors often. They see an ad for a new medicine for their disease, they go to the doctor, it works better, and hooray.
Maybe doctors should be able to send out email blasts to people, but I'm guessing that's not HIPAA friendly. Also, I've had online ads aimed at oncologists served to me for different medications.
I think the fact that there are both TV ads for cancer medications and online ads aimed at oncologists says a lot about the fact that a ton of doctor's aren't keeping up with what's new, even in something as critical and limited in scope as specific cancers are.
Gilead's R&D costs for Truvada as PrEP were literally almost zero. They paid none of the costs for actually conducting the trials.
Their only contribution was that they donated the actual pills used in the trials - in other words, the unit price of 30 pills per person for the duration of the trial.
You are quoting a corporate press release that was written in response to an editorial criticizing Gilead, which was based on my colleagues' work.
This is a great example of how easy it is to fall for propaganda, because not a single thing in your link refutes what I said! They spent money developing Truvada as a treatment for HIV, then made that money back in record profits for nearly a decade. Only then did clinical trials for PrEP begin, and for those, Gilead donated only the production costs of Truvada (which are minimal). They did not spend any money in actually conducting the trials - which, as pharmaceutical companies are generally very quick to point out - is where most of the costs of bringing a drug to market are.
Gilead is claiming that, when it spent half a billion dollars to acquire a biotech company that went bankrupt, 100% of the money in that transaction should as "R&D related to Truvada". This is preposterous. Neither the SEC nor the IRS would endorse that accounting, which is why you're seeing it in a press release and not their 10-K.
That's a ridiculous claim even when you're talking about the development of Truvada, but that's not even the question at hand. The actual topic is how much was paid for the development of PrEP, which came nearly a decade later, and for which Gilead paid nothing but the per-unit costs of production.
The $1.1 billion figure is for Truvada total, not for PrEP specifically. It’s perhaps notable that Gilead chose not to break that down, given that the original claim they were responding to was about PrEP specifically.
> The $1.1 billion figure is for Truvada total, not for PrEP specifically. It’s perhaps notable that Gilead chose not to break that down, given that the original claim they were responding to was about PrEP specifically.
And even then it's a dishonest claim. Half of that $1.1 billion is the amount of money they paid to acquire another biotech company in a firesale. It's beyond disingenuous for them to claim all of that towards the amount they spent developing Truvada, since they received way more assets in that sale than just the patent for one drug.
I just want to point out that the government has assumed the role of telling everyone how to take risks for its economy, and literally all you have to do is do that, successfully, and it will privilege your rewards by reducing risk on profits or reducing taxes
This is not controversial when you look at the state’s role in these outcomes
It’s life-saving medication. It should be freely available to everyone, period.
If we’re not willing to question the degree to which big pharma ought to profit off of controlling access to scientific miracles, the least we could do is use taxes to subsidize the cost - “I can’t afford it” should not be a reason to not be on PrEP.
Anyone should be able to walk into a CVS and walk out with 2-1-1 dose, as easily as they’d pick up the morning after pill, or a bottle of aspirin.
To find the correct pricing you just check how much shareholders make. If they get unreasonably high return on their investment that means the company is overcharging.
Tax shareholders on their gains and rebate customers if the company doesn't adjust the price.
The patent system literally grants monopolies, on purpose. I don't know why people are surprised when patented things are priced like there's a monopoly exploiting their customers, because that's exactly what's happening and everyone knows it. But somehow people never seem to come to the conclusion that granting monopolies is not the ideal way to incentivize things.
Maybe it is if the alternative is those things you granted monopoly on wouldn't exist. With drugs especially it's a difficult proposition to spend time researching if the day after you make your pill and sell the first one the next guy can just sell it too. So we need a larger change than just modifying the patent system for medicines, we'd also need to change the way we fund pharma research and after having thought about it a lot I don't have a solution. I agree with the problem you mention, but the solution isn't simple.
There’s no reason pharma research should be for profit. The researchers aren’t doing it for profit, they would do it either way, the only thing private pharma brings to the table is price gouging.
Citation needed on "the researchers aren't doing it for profit". All drug companies have a bunch of them, more than wall street types running around. Most of them enrich themselves with biotech stock bets, insider trading, regulatory capture of national agencies etc. Why do you think somehow people that go into pharma research are different from people in any other industry?
If you speak to anyone in the field, their goal to get to a point where you having a patent or two giving you a passive income stream. You can't do it if you just public domain your work.
Maybe my understanding is wrong, you’re telling me researchers keep the rights to patents they develop under the employment of pharmaceutical companies, and profit off of licensing? If that’s the case I was wrong.
But as for your other point, yes, researchers are different from people in other industries because of the high barrier of entry into the field through years of schooling, and the uncertainty of the work. Anyone that’s motivated primarily by money wouldn’t go into pharma research, they’d go into CS or finance straight off university.
Of course, that doesn’t mean they don’t want money. If you can do a job you love and get rich off it that’s the dream. And there’s no reason the public sector can’t pay enough to motivate researchers.
> But as for your other point, yes, researchers are different from people in other industries because of the high barrier of entry into the field through years of schooling, and the uncertainty of the work. Anyone that’s motivated primarily by money wouldn’t go into pharma research, they’d go into CS or finance straight off university.
Careful with generalizations like this, you're not far from "all CS people are neckbeards" with this "all researchers are good people". My rule of thumb is "every large enough group of people is very similar to any other". This comes from the Central Limit Theorem.
Regarding you thinking researchers don't get paid from patents, here you go:
> “Recently, our organization at OpenTheBooks.com forced NIH to disclose over 22,100 royalty payments totaling nearly $134 million paid to the agency and nearly 1,700 NIH scientists,” Adam Andrzejewski, the group’s founder and CEO, wrote in a May 9 report. “These payments occurred during the most recently available period (September 2009 – September 2014).”
The article is mostly about a specific claim they made about Fauci but you can see even just at the NIH there's a lot of money being made personally by researchers or ex-researchers like this. Which is not inherently bad, but we should keep it in mind.
Stop putting words in my mouth. Engage with my argument, not with the straw man you constructed in your head.
Ok, I’m happy about your theorem, but there’s a reason only tall people play in the NBA.
And like, are you even reading what you’re posting, or are you just googling for articles that support your position? We’re talking about private pharmaceutical companies and you’re linking an article about a public research institution.
See, blaming private companies for the consequences of government-granted monopolies is exactly the kind of thing I don't understand. The government is handing out permission to price gouge. On purpose!
How did governments create pharmaceutical monopolies? And, if they did, why does that make the companies killing people by charging exorbitant amounts for drugs free of guilt?
Governments create pharmaceutical monopolies by granting parents that make competition illegal. They do this explicitly so that companies can raise prices, to incentivize and fund drug development (which other government regulations make more expensive). Companies are using the system as designed and intended by the government.
Nobody would develop drugs under today's ridiculously expensive process without some kind of very large incentive, so those life saving drugs wouldn't exist without those high prices. But obviously the system is terrible. Costs could be lower to reduce the need for the price gouging incentive, and there are other incentive structures that could be used instead of granting monopolies that wouldn't have as many terrible side effects. (Price gouging is far from the only issue with patents.)
I see what you mean, but it’s not that simple. Sure, the government of a country issues a patent, but that patent is enforced by the WTO, not by the individual country.
Sure, an individual country can decide to break that patent, but if they do that they’re punished by the WTO. And large pharmaceutical companies have a large influence on the WTO through lobbying, and the revolving door from public and private executive positions in rich countries in Europe and the US.
So it’s not like these companies aren’t culpable either.
One more thing, you say that no one would develop drugs without some kind of very large incentive.
The incentive to governments is making sure their citizens don’t die. Even ignoring the ethical side of it, you can’t tax a dead person, so it’s in the governments best interest to develop drugs, and charge as little as possible for them for its own citizens.
The WTO is a creation of governments and ultimately under their control. If the US wanted to change how medical patents work it could absolutely do so. These are government failings and blaming them mostly or exclusively on private companies is ridiculous.
Well yeah, but not all governments are equal. Sure, if the USA wanted to it could do whatever it wanted to, but that’s not the case for any other country in the world.
And the same people that wrote those legislation are also the ones running big pharma.
In the Netherlands until recently you could get it for ~$10/mo (now ~$20). We have a whole website naming prices in different pharmacies around the country.
Like the other commenters allude to, how would you like software mandated to cost just 10% margin over COGS? Do you think selling cloud services for 10% more than the cost of server parts is going to be a business when there's thousands of software engineers in R&D needed?
I would love that, as long as the cost includes that R&D and those engineers, the actual bits might be immaterial but the engineer salaries are part of the cost of the goods.
The problem is that we're being told that the cost of insulin is $270 per vial, or that Daraprim used to estimate its cost per dose at 90% of $13.50 and then Shkreli decided to raise it to $750.
The Shkreli case has nothing to do with the rest. He was playing the insurance companies and there isn't a single person that went without the medicine due to the cost. Almost nobody takes this medicine.
It's true. Harvard education costs $300k, so that engineer's lifetime earnings can be $300k plus some small margin so that he does not price gouge. Community college engineer can be paid $2k+small margin.
I see. So all software engineers can charge what they want until the moment they join another software engineer. The moment the two of them work together on a shared enterprise, their margin must be capped.
As an employer, hiring single-person LLCs provides such a strong advantage in this universe over hiring employees. The former can't charge you more than a small percentage. The latter can charge as much as they want. I suppose we would all be like Uber drivers.
Honestly, 10% above costs would put a lot of people far more into the black than they currently are, because you are failing to account for ongoing expenses which raises said cap by a lot. To say nothing that most folks are struggling to make rent and buy food; I think they would like such a deal.
Software devs in the US are not struggling to make rent and buy food. More likely for them to have one or two airbnb side hustles than be starving. Yes, some have it rough but I'd wager the bell curve puts professional devs in the better-off-than-most boat
Oh no you misunderstood, it’s not 10% more than your costs, it’s 10% more than what the cost for a person to live a dignified life should be. So this would really only take money away from people that earn way more than needed.
If it's like every other IP-encumbered drug, the price will be approximately "the value the recipient places on HIV resistance," which is probably close to what's being charged now.
Why would they give up the profit? What's your rationale here?
Cure = $X
If the treatment is daily then it's $X/365 if it's monthly the price is $X/12 if it's twice a year it's $X/2
Imagine being an exec at that company and being like "let's give up 50/52 of our profit because it's more convenient for the patient"? How many hours would it take between giving that speech and getting fired, do you think?
Please forgive my lack of understanding. This appears to be a great achievement.
Is there any risk that a Lenacapavir resistant strain would rise up in many years as a result of treating a large portion of the global at risk population (estimated to be 60m people receiving the injection to materially lower global HIV rates)?
Sort of like how antibiotic resistant bacteria rates seems to evolve out of the use of antibiotics? Or is that not a thing and Im just clueless?
"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, “making them defective so that they are not able to infect other cells.” Therefore, it works in both early and late stages of the HIV life cycle to disrupt replication."
Since the drug works in two ways, it would be difficult for the virus to adapt. Similarly to how the current commonly prescribed PrEP regimen (Descovy or Truvada) is two different drugs in one pill and has not lead to any significant rise in resistance.
Yes that is correct, it's pretty easy to create escape variants in the lab. I don't think people should be doing it with virus like HIV and SARS, but they do.
I'm surprised people are still making that argument even after the pandemic showed us the risk is nowhere near worth the reward. Regardless you need to create a vaccine for the discovered virus (which can take less than a week, as was the case with covid). And then you still need to go through months of human trials.
I was hoping we were done risking starting pandemics by purposefully creating new deadly viruses.
Agreed. Making super viruses to show what could possibly happen, however unlikely, is the epitome of hubris. But boy is it a great to get funding.
I do wonder what the calculus is when comparing the chance nature could mutate and successfully introduce itself to the human population vs the chance of it escaping a lab after being created by humans to study gain of function, etc.
the jury is still out on whether COVID originated from a lab. it seems very possible, but there is still little evidence that proves it was created in a lab.
Well, we do know COVID did leak from a lab in China at least one time: in 2021, a researcher in Taiwan was bitten by an infected mouse and contracted the disease.
Edit: My bad, as far as public knowledge goes, coronavirus leaked three times in China (SARS coronavirus 2x, COVID 1x), and once in Singapore.
As for Wuhan in November 2019, the Chinese government took several actions at that time which you would expect to be taken in response to a biosecurity incident: visits from biosecurity officials, remedial biosecurity training, and (coincidentally) government simultaneously began work on a COVID vaccine.
Only circumstantial evidence, though... so... ¯\_(ツ)_/¯
“You may be surprised to learn that of the trio of long-awaited coronavirus vaccines, the most promising, Moderna’s mRNA-1273, which reported a 94.5 percent efficacy rate on November 16, had been designed by January 13. This was just two days after the genetic sequence had been made public”
Isn't there a big difference between "designed" and "developed"? For instance the whole testing phase?
Which doesn't mean it is not impressively fast, but still it's not done in a week. Plus testing the covid vaccines was quick because there were many many people to participate in the tests.
And where comes the human part in the equation? That some people think they are so smart no mistake can ever occur, like viruses escaping into the wild, proofs their lack of understanding.
HIV has a crazy high mutation rate, way larger than other viruses like SARS-COV-2 or the influenza virus. In an infected untreated human, you have at least one copy of the HIV virus produced for each base pair mutation within a day or so. In other words, if there is a single base pair mutation that makes HIV resistant to a single drug, HIV will adapt quickly. So that's why they quickly discovered to do double therapy, and nowadays one does triple therapy even, so that a virus has to randomly become resistant to three drugs at the same time.
this could happen, but hiv isn't contagious like the flu so even if there'll be an individual with such a strain - how likely it'll pass to others?
Also, this drug limits replication, meaning there'll be less and less mutations over time compared to a fully spread virus
> Please forgive my lack of understanding. This appears to be a great achievement. Is there any risk that a Lenacapavir resistant strain would rise up in many years as a result of treating a large portion of the global at risk population (estimated to be 60m people receiving the injection to materially lower global HIV rates)?
Not really. This same principle has been used for over a decade. The only difference here is that the previous version of injectables needed to be administered every two months, whereas this can be done every six months.
HIV drug resistance is a real issue, not sure why other comments are dismissing the risk of resistance. The risk of resistance is why HIV positive individuals take a cocktail of drugs, and why PrEP (Truvada or Descovy) requires regular HIV testing (because if you end up positive you need to upgraded to a cocktail of drugs).
PrEP is incredibly effective, and even better than condoms at preventing HIV. There's various reasons it requires regular testing:
- While very effective, it requires people to actually take it consistently, which is why the injectable form is better for some than the pill.
- PrEP is not without side effects for a small portion of its users. In some cases it can cause bone density loss, or kidney damage. These tests are intended to catch any issues before they cause any permanent damage.
- Since people are coming in to get tested for the aforementioned issues, they also run a full STI panel. This is great and it means those on PrEP (And those managing HIV) are tested more frequently than the general population, and are less likely to transmit an STI than those who don't come in for regular testing.
(Joke) I'm still waiting for bacteria to evolve a resistance to boiling!
(Seriousness) Different infectious agents can / can not evolve around their vaccines. We don't get yearly polio shots, we do get yearly covid/flu shots.
(Speculation) It's probably too early to tell if there's a way for HIV to evolve around this, but it might have something to do with how effective we are at killing HIV in our population to begin with.
Polio can and does mutate almost instantly around the vaccines, but since some of the vaccines are live polio anyway people don't really care. "Mutation" is not really a word that matters, what matters is if a variant is causing problems.
On rare occasions the live vaccine actually reverts. Polio is an amazing story because the live vaccination campaign may have had collateral impact on the families of the vaccinated as they shed particles.
Rare? It's in almost everyone who gets the vaccine. I don't have a direct citation, but I don't think it's generally doubted, though it's not something that's easy to do a direct controlled test on.
Without mention of the number of study participants or risk, I was a bit suspicious, but it's not a tiny sample size, and not a low-risk group. From the paper:
> Among 5338 participants who were initially HIV-negative, 55 incident HIV infections were observed: 0 infections among 2134 participants in the lenacapavir group
The infections in the control groups were in people taking other preventative medication, not nothing.
In terms of protecting oneself, what are the actual steps? (E.g. if you're HIV- but are participating in activities either directly with someone who is HIV+ or whose partner is HIV+.)
Do you schedule a doctor appointment and ask for something specific? And is there anything else to do, such as something over-the-counter?
There's a dizzying array of terms to learn in this space. PrEP is apparently different from PEP, which I think is also unrelated to what this article is talking about. It'd be nice if someone put together a 2024 guide for what the latest preventative / protection mechanisms are.
Assuming you do not currently have a viral load of HIV, you can meet with your provider, indicate that you are at risk, and request a prescription for PrEP [1] (Planned Parenthood can assist with sourcing if you don't have a PCP or other stable medical providers). Longer term, it is likely there will be a shift to a twice yearly injectable (Gilead’s Lenacapavir) [2]. State of the art is an undetectable viral load due to antiviral treatment means you cannot transmit to others [3] [4] [5].
Not medical advice, educational purposes only. Seek a medical professional's guidance for your personal circumstances.
> Longer term, it is likely there will be a shift to a twice yearly injectable (Gilead’s Lenacapavir)
That's debatable. Injectable PrEP has been around for years already (Lencapavir is not the first, just the most recent). Lencapavir has also not yet been tested on all at-risk groups, so unlike other forms of PrEP, it's not a universal solution because it cannot be prescribed to all candidates.
Given the price, which is quite high even with the programs Gilead has said that it will issue to reduce the cost, it remains to be seen how widely-used Lencapavir becomes outside of specific markets.
The problem I think really comes down to there being a generic Truvada.
Insurance for a bit seemed fine with covering Descovy but it seems that is less of a case now since it’s so much more. I would expect the same with a shot like this.
However I would hope that the added benefit of not needing to worry about adhering to taking it every day could outweigh that financial cost for insurance.
I recently switched insurance companies and my new one covers Truvada completely, not even a copay. It’s honestly kinda wild I pay more for my Adderall than I do prep. Obviously I don’t know for sure but I have wondered if it is related to it being preventative and the potential alternative cost makes it smarter to remove any barriers.
Almost all health insurance companies in the USA are required to fully cover PrEP, including Descovy. This doesn't stop health insurance companies from trying to deny you, of course. You would have to appeal the denial all the way up to your state's department for health insurance, but you would definitely win.
EDIT: I was mistaken, this only applies in California.
> Almost all health insurance companies in the USA are required to fully cover PrEP, including Descovy. They aren't even allowed to require that you try (generic) Truvada first before trying Descovy.
They are required to cover PrEP, but that doesn't mean that they are required to cover Descovy specifically. If they cover Truvada and all associated labwork or outpatient visits without any out-of-pocket costs for you, that's sufficient to comply with the law.
> This doesn't stop health insurance companies from trying to deny you, of course. You have to appeal the denial all the way up to your state's department for health insurance, which you will definitely win.
Having helped many people who've been in this exact situation, it's unfortunately not a given that you will win (you have to play your cards exactly right), and most people who need it can't afford to pay over $2000/month for the several months it takes for this to happen[0].
The most likely scenario is that the insurance company wins, because you give up.
[0] The insurance company has something like 30 days to respond for the first appeal, then an additional 45 for the second and third rounds, and that's assuming everything happens on schedule and you respond to everything immediately.
There is also an emerging market for companies that will help you fight health insurers, and I'd have to imagine that they have some playbooks or can develop them for common situations.
And if not, maybe there should be. I saw some ugly shit in my days working for a company that wrote software for some of the bigger insurers.
That… is good to know. I knew they were required but figured generic Truvada was the requirement.
Well kinda irrelevant. My previous insurance loved to deny things, it’s why my company changed.
I worked with my doctor, tried multiple times to get them to cover Descovy (I struggled with the larger pills, I finally just forced myself to get used to it) and was never successful. Just gave up.
See my sibling comment. GP is half-correct. They are not required to cover Descovy specifically. Covering Truvada is sufficient to comply with the law (assuming they are also covering all associated labwork and outpatient visits, and not requiring you to pay anything out-of-pocket for any of those).
> The problem I think really comes down to there being a generic Truvada.
Truvada has been generic for about six years now.
> I recently switched insurance companies and my new one covers Truvada completely, not even a copay. It’s honestly kinda wild I pay more for my Adderall than I do prep.
That's because under the ACA, insurance companies are legally required to cover PrEP at no out-of-pocket cost, without any cost-sharing, copays, or deductibles applied. This also applies to associated labwork and outpatient office visits.
Unfortunately, many insurance companies ignore this requirement, and it's very difficult as an individual to get them to comply.
I’m confused. The parent comment said “longer term,” and you went on to discuss how it is not going to be used in the short term, due to the need for more testing and cost.
Cost comes down over time, and more testing occurs over time, somewhat by definition.
So… what specifically is debatable about the longer term?
> Cost comes down over time, and more testing occurs over time, somewhat by definition.
Truvada has been around for over twenty years, and generic for 4-5 years. It still costs $2000/month list price.
More testing doesn't just magically happen either. Gilead has chosen for years not to pursue testing, let alone approval, for Descovy in various groups excluded from the original clinical trials. They've decided it's not profitable enough for them. The same could very easily happen with lencapavir, and in fact there's good reason to suspect it will.
Why is it so expensive? And is it covered by insurance? If so, then I'm not sure the list price matters all that much from a 'to most people' perspective, even if there is a moral argument to be had here (in which we'd probably agree).
I'm not entirely sure what the argument is, though - is it just the cynical argument of "well, these companies don't care about solving problems, just profit, so they're never going to do anything with it"? If so, then at least I understand your argument, even if I don't necessarily agree.
> Even when viral load is undetectable, ... may have detectable HIV genetic material in ... semen, but there is no scientific evidence that such material is associated with HIV transmission.
Transmission has never been found when the number of copies of the HIV RNA are below 200 copies/mL--the quantity of virus matters.
For context, the typical ejaculation from someone untreated contains between 10,000 and 1,000,000 copies/mL. With treatment, the average is 1-10 copies/mL.
Besides HPTN 052, there have been three other studies--PARTNER, PARTNER 2, and DISCOVER, of real-world (condomless) usage in mixed serotype couples
> Findings from the breakthrough NIH-funded HPTN 052 clinical trial, a decade-long study involving more than 1,600 heterosexual couples, offered clear-cut evidence that ART that consistently suppresses HIV also prevents sexual transmission of the virus. In 2011, the HPTN 052 investigators reported that starting ART when the immune system is relatively healthy, as opposed to delaying therapy until the immune system has been weakened by the virus, dramatically reduces the risk of sexually transmitting HIV. The protective effect of starting ART early was sustained over four additional years of follow-up. Importantly, when viral loads were measured, no HIV transmissions were observed when ART consistently, durably suppressed the virus in the partner living with HIV.
Wild speculation is that the genetic material you mention is inactivated and therefore unable to transmit the virus, but is still detectable. I am just an internet rando surfing the knowledge graph, but the science appears sound.
I find "absolute minimum" an unfortunate choice of phrasing when the process necessarily has large elements of randomness and could in principle well proceed from a single cell getting successfully infected.
But it's interesting to note that the way HIV generates its infamous genetic variability can result in a remarkably large fraction of the virions being mutated beyond viability.
The infection risk would have to involve a factor of virions getting to a susceptible cell without getting destroyed anyway of course, but given that many of the contenders might not be capable of infecting even if they get there it seems even more understandable if one would usually end up with 10 as the number needed to satisfy some chosen level of statistical significance.
I don't buy U=U, I've not seen a proper impossibility proof re. provirus mutation. There's probably infections drowned out against the background rate.
I don't think I am, in the provirus state you can think of it as essentially a DNA virus in an inert state, and if the DNA fragments the right way it would turn into something similar to a bare DNA vaccine. That design of vaccine essentially does not work, but they have an effect that is not literally zero. I think there's enough holes in the layers of "Swiss cheese" that normally prevent this chain of events that U does not literally equal U.
Edit: right, I'm also assuming the possibility of provirus mutation before this chain of events, and I don't think anyone can deny at least the mutation of HIV before it becomes a provirus.
Are you a virologist, epidemiologist or other specialist with peer-reviewed research pointing in the direction opposite to the conclusions in the paper above? If so, you should publish your findings because that would be a huge refutation of current knowledge and would possibly help the epidemiology of transmission in the greater public.
Until then, I'll take the word of public health practitioners who've been steeped in the field for their entire careers. Their work has been significant enough to be published in Lancet which is a pretty good signal to this layman (though with a bachelor's of science in an unrelated scientific field, so no stranger to reading primary literature).
I probably could write something, but HIV is an epidemiologist's game at this point, and I honestly think the epidemiologists want to say HIV can't transmit in ways that the Hepatitis B virus, a DNA virus, has clearly been demonstrated to transmit. If you press a virologist in private I'm not sure they'll stick to "can't", especially after the COVID-19 virus mutation rate fiasco, and, though not a virus, the prion situation.
I think "can't" deserves at least something physically (as in physics) unlikely, not something that's been demonstrated in a DNA virus previously (and like I said, HIV in provirus form is not unlike a DNA virus).
>Their work has been significant enough to be published in Lancet which is a pretty good signal to this layman (though with a bachelor's of science in an unrelated scientific field, so no stranger to reading primary literature).
i've no opinion on the topic at hand, but I would urge you to find a plethora of signals to form your opinions.
The Lancet has been responsible for quite a few negative 'public health' trends.
The Lancet is responsible, at least partially, for the whole 'vaccines == autism' thing of Andrew Wakefield's; and even ignoring that they have a history of poor review and retraction of work that ends up either being entirely wrong, or guilty of experimental misconduct.
In 1992 they published stuff that suggested a causal link between HIV infection and the oral polio vaccines.
In 1998 they published a (big tobacco funded) peper indicating that second hand smoke doesn't have as much risk as earlier thought.
In 2000 they published a study that claimed that St Johns Wort was as effective an anti-depressant as conventional SSRIs and TCAs.
Just because something has become 'prestigious' doesn't mean it should be trusted wholeheartedly.
This isn't about the Lancet specifically. It's about someone on the internet challenging the overwhelming medical consensus without providing a shred of evidence to support their claims. I can assure you that 'people saying things on the internet' have a far worse record on medical matters than the Lancet, or the medical consensus more generally.
You could try asking a virologist if they think it's possible for the HIV-1 provirus to ever be in a state where it could theoretically be infectious given the right DNA fragmentation.
PEP means "post-exposure prophylaxis"; PrEP means "pre-exposure prophylaxis". You take PrEP regularly (if you know you're at risk due to sexual habits etc whatever), but only take PEP in response to a specific possible-exposure event (and not already on PrEP). You want pre-exposure instead of post-exposure because post-exposure is very hard on your body and makes you feel sick.
Clinics are pretty good. But in general, if you’re a woman in a first world nation your odds of getting it are really low, unless you do significant amounts of anal sex with bisexual men or inject drugs.
Same thing with men. Straight men aren’t at much risk. Bi and gay men are at high risk.
If you have a hiv+ partner, prep is good enough to keep you safe. Just take it always as prescribed.
Pep in for when you may have been exposed, and you need to get it as soon as possible. It’s like a morning after pill. Within 72 hours of exposure but sooner is better.
Then for anyone who does unprotected casual sex, there’s doxypep which reduces likelihood of bacterial stds by a lot, so gonorrhea, chlamydia, and syphilis.
If you want a person to explain this to you in real life, there’s different clinics in every American city that would love to take the time to teach you about all of this. Part of their funding is to educate
PrEP - An HIV negative person taking Truvada or Descovy once a day to prevent HIV infection.
PEP - An HIV negative person taking a course of antiretrovirals within 72 hours after exposure to HIV to prevent HIV infection.
This article is referring to injectable PrEP. This is already available via an injection every two months and is typically used in populations that can't be expected to take a pill every day (drug addicts, etc.). The article is referring to a new form of injectable PrEP that extends this to once every six months.
> This is already available via an injection every two months and is typically used in populations that can't be expected to take a pill every day (drug addicts, etc.).
That is a pretty bold parenthetical statement. Not only is it not true that "drug addicts" can't be expected to take a pill every day, but neither cabotegravir nor lenacapavir are tested or approved for HIV acquired through non-sexual means, which makes them a poor choice for PrEP for "drug addicts" compared to oral forms, which are effective against all forms of HIV transmission.
Source: former counselor and educator for HIV and substance use
> The general population can't be expected to take a pill every day, what would make anyone believe people with SUD are able to?
The general population does take PrEP regularly enough to be protected. You seem think that people with substance use disorders are excluded from that, and that belief is grounded in stereotype and bias, not science.
People with substance abuse disorders are not binarily excluded or included from adherence to taking a daily regimen. However, it is not an unreasonable expectation that someone shooting heroin every week in a flop house is less likely to take a daily medicine than the average population.
The belief that drug addicts can't be expected to take a daily pill is not grounded in stereotype and bias, it's a realistic and down to earth perspective that for some of them, their addiction is crippling their ability to function.
This kind of unrealistic thinking from up on a high horse is exactly what I'd expect from a former HIV counselor/educator, hence our historic inability to get this virus under control.
What I have noticed is that in most situations saying "PrEP" is enough. For my doctor that meant discussing Truvada, Descovy, and what is just kinda dubbed "Injectable Prep". This aligns with most apps also just saying "on prep" with no distinguishing between what prep.
I would imagine that if/when this comes to market it would likely similarly fall under "Prep" for the general community and then you discuss the specifics with your doctor.
Edit: There is also Doxypep (I just say Doxy), which while related to STD's is not related to HIV.
There are people announcing their PrEP status on dating apps so they can raw dog with strangers? Have people forgotten that there are plenty of STD besides HIV?
I think this is highly problematic and lifestyle PrEP seems to be counterproductive as a public health measure.
But I am open to arguments that I’m wrong. It’s possible that I am biased as a monogamous heterosexual who has grown up in a culture where sex without condom, especially outside committed relationships, is generally frowned upon and 1980-1990s HIV scares are still in the consciousness of people.
> lifestyle PrEP seems to be counterproductive as a public health measure
No. Preventing HIV is not "counterproductive" because maybe some people got chlamydia when they shouldn't have.
First off, PrEP is more effective at preventing HIV than condoms. Doing away with PrEP to "improve public health" WILL give more people HIV.
Second off, people don't always use condoms. We can sit here all day and argue about what people should do or morality or discipline or whatever. None of that matters. What matters is what people ACTUALLY do. We have not yet unlocked mind control so we have to work within the constraints of humanity.
Third, people who do use condoms don't actually use them right, generally. Syphilis, chlamydia, and gonorrhea are all transmitted through oral sex. Nobody, even heterosexuals, uses a condom for oral sex.
Lastly, other STIs are actually very treatable. While they sound big bad and scary, they're nothing like HIV. 5 days of antibiotics and a runny nose is not equivalent to a lifetime of being HIV positive. People treat other STIs as less serious because they are, especially if you get tested regularly. Gay men and especially gay men on PrEP get tested very, very regularly. The odds of long-term syphilis side effects or whatnot is basically 0.
Nobody’s giving or getting head with a condom. People who stay on top of preventative measures tend to not bother with condoms since PrEP became prevalent, because the rest of them you can get with or without a condom due to oral.
Preventative:
1. Gardasil 9 (vaccine against 9 strains of HPV, prevents genital warts and cancers caused by HPV)
2. Monkeypox vaccine
3. Meningitis ACYW vax
4. Meningitis B vax (35% effective against gonorrhea)
5. doxyPEP (two pills of doxycycline taken after sex, 90% effective against syphilis, 80% chlamydia, 50% gonorrhea)
6. PrEP (prevents HIV infections)
7. and the usual suite of vaccines against the rest like hepatitis A/B, mumps etc
You’ll notice all of these give you far more protection than a condom would. Again, especially since oral is a thing.
Treatment of the bacterial ones (which transmit through oral too):
1. syphilis - butt shot of penicillin
2. chlamydia - 1/2 pills of an antibiotic
3. gonorrhea - a week of doxycycline pills or one butt shot of ceftriaxone
Remaining unpreventable/untreatable one is HSV. Half of the population has it. Condoms dont prevent it either.
Hepatitis requires blood contact and as such is not necessarily considered an STI, but hepatitis c is curable these days thanks to DAAs taken over the course of 8-12 weeks, and a/b variants have vaccines.
Thank you for adding this here, I was working on compiling something similar for another comment on the thread. This is pretty much the gold standard and yeah those that keep up on preventatives and testing are usually the least likely to pass anything along. More information is better, not less! These puritanical views on human sexuality, like the comment above yours to which you're responding and others, only cause more hurt and don't really have any sort of deterrent effect. Peeps be fuckin', nothing you can do to stop it besides get the best info and treatments out there.
Hi, I wanted to clarify here that I don’t have „puritanical views“ on human sexuality, but I am aware of my bias and wanted people to give me further information. I could already „smell“ that I was wrong with my perception, hence the comment.
I didn’t want to cause any hurt with my questions, please assume naïveté and not malice.
"Lenacapavir works by binding directly to the interface between HIV-1 viral capsid protein (p24) subunits in capsid hexamers, interfering with essential steps of viral replication, including capsid-mediated nuclear uptake of HIV-1 proviral DNA, virus assembly and release, production of capsid protein subunits, and capsid core formation[1]... It functions by binding to the hydrophobic pocket formed by two neighboring protein subunits in the capsid shell. This bond stabilizes the capsid structure and inhibits the functional disassembly of the capsid in infected cells.[2]"
In other words, it prevents the virus' protein shell (capsid) from being built properly, which in turn prevents the virus from properly opening ("uncoating") once it enters a host cell.
> It functions by binding to the hydrophobic pocket formed by two neighboring protein subunits in the capsid shell
That's entirely cool to me, it operates by exploiting an "incidental construction feature" of the capsid and not targeting any specific feature in and of itself?
It's HIV itself that "knows" where the nucleus is and is actively trying to get there once it's inside your cell. It does this by walking itself along your cell's microtubial network. It would be fascinating if it wasn't so deadly.
by preventing viral capsid assembly, as noted in the article.
Once bound to the P24 capsid protein, the drug also interferes with other stages of the virus’ lifecycle[1]:
>Lenacapavir is a multistage, selective inhibitor of HIV-1 capsid function that directly binds to the interface between capsid protein (p24) subunits in hexamers. Surface plasmon resonance sensorgrams showed dose-dependent and saturable binding of lenacapavir to cross-linked wild-type capsid hexamer with an equilibrium binding constant (KD) of 1.4 nM. Lenacapavir inhibits HIV-1 replication by interfering with multiple essential steps of the viral lifecycle, including 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 capsid protein subunits), and capsid core formation (by disrupting the rate of capsid subunit association, leading to malformed capsids).
30 years ago in South Africa there was fear about contracting HIV (and so inevitably dying) through the ear via public telephones (which is ridiculous and impossible). Doctors in trauma wards were terrified of contracting the disease. Huge amounts of stigma and misinformation, and little hope.
It’s amazing that since then:
- A treated HIV diagnosis no longer necessarily changes your life expectancy.
- Your HIV negative partner or unborn child will not necessarily contract the disease, if treated.
- Treatment adherence requires just two visits a year.
- Doctors have a ready solution in the case of accidental potential transmission.
- I can’t remember the last time I saw a public telephone.
I was mind-blown when I learned we were at a point where we could realistically talk about eradicating HIV. Am not a Tory by any stretch of the imagination but props where it's due to them for saying it out loud: no new HIV infections in UK by 2030. As far as I understand the current government are committed to this plan also.
Of course, no new infections in UK != eradication, which is the next step. I had not heard of Lenacapavir - this is amazing news from Munich.
With regards to HIV and Aids, Nobel price winner Kary Mullis (inventor of PCR test), made many interesting remarks. I thought that was an interesting interview.
Your response makes me wonder ... In the interview Kary Mullis mentions that no scientist ever has been able to proof that HIV causes Aids. He also mentions that test monkeys have been injected with HIV and these monkeys didn't develop Aids. Actually, these monkeys got rid of the HIV after some time.
I guess many years have passed since this interview (from 1996).
My question to you: is there a scientist now that has been able to proof that HIV is the cause of Aids? Because he also mentions a scientist who'd do such a discovery would be famous, maybe Nobel prize winner, etcetera.
P.S.: From the interview it doesn't seem Kary Mullis denies Aids. Kary mentions Aids is likely caused by anal sex in some way.
They stopped the study because of the incredible efficacy and lack of side effects. This was a phase 3 clinical trial so they have already cleared substantial hurdles in safety requirements (clinical trials are about both efficacy and side effects).
But for argument’s sake, there are even more sides than efficacy and safety: there are substantially different risk profiles for different potential patients, and a long acting treatment with no daily pill is more valuable for some people.
One of the reasons that long acting injectables could have a big impact on transmission in Africa is because there’s stigma around PrEP usage, especially for women. Obviously, there is now a big conversation about the cost and who pays, but the potential here is indisputable.
> They stopped the study because of the incredible efficacy and lack of side effects.
Are you aware that historically when this has happened, it almost always turns out to have negative side effects and marginal efficacy?
Don't you think an easy con is to flip a coin 3 times, and if you get heads all 3 times, tell everyone it always comes up heads, and there's no need to continue to measure it, but just to trust them?
Usually when a study is halted early it’s because of obvious harm to the experimental group from the treatment which means there would be no possible benefit and it would make continuation unethical.
A meta analysis of early stopping in randomized clinical trials has found no evidence that early stopping hides side effects or inflates benefit—and I challenge you to produce any examples of a phase 3 trial of an infectious disease treatment that was stopped early which later showed unduly harmful side effects for marginal benefit.
This trial showed 100% efficacy.
A major consideration of RCTs is also the benefit denied to the public by withholding a viable treatment. HIV remains a global epidemic with no existing good solutions for poor countries.
Your account is new and has no profile and for all we know could be a bot.
However, in adhering to the HN guidelines [0] I must "assume good faith".
And indeed, you provided an excellent, intelligent reference! Very interesting paper and debate.
In the paper the authors review the debate on early stopping, and then created a model/simulation to examine what one might expect.
I should note that the paper came out in 2016, which was before the December 2020 early stopping of the COVID vaccine trials, a real world example of an early stopping debacle, where trials were stopped and then efficacy turned out to be vastly less than originally reported (even worse than the "29%
exaggeration of effect" Bassler et al originally reported).
I think your argument has convinced me that my position is not correct. However, it has not convinced me that early stopping is correct either. I think the obviously dumb thing is having these rigid trials, and a far better idea is to have real-time adjustable ongoing data collection and experimentation that never stops.
I don’t think anything is going to be as devastating as 60%+ of Eswatini’s women between the ages of 25-39 being HIV+. Anything that can put a dent in that is going to far outweigh any potential risks and side effects. That whole country is going to be dead in 5-10 years unless they all get a daily dose of ART for the rest of their lives.
On a side note, that number is absolutely unbelievable considering that heterosexual intercourse has a 0.08% chance of infection. Do they all have 100s of sexual partners and tens of thousands of sexual interactions before they’re 30?
This is an historic achievement with huge benefits, particularly for Africa.
AFAIK, Gilead hasn't detailed any commitment to making it available to all who need it. There's been talk of $4K -$42K yearly price. Gilead just this month is promising regulatory submissions for approvals soon. The drugs sounds quite complicated and hence difficult to manufacture, perhaps making it an enduring franchise.
The original post is raising a most interesting question: in a world where preventing infection is possible, what's the standard or incentive for a vaccine? It's rare to get 100% prevention from a vaccine. The incentive would seem to depend only on cost, and any vaccine developer would know that Gilead can likely lower cost at will, making it impossible to recoup vaccine development costs.
A lot of health care problems are undermined by the profit motive angle.
I don't know how to solve that because there's no such thing as a free lunch and the people developing solutions deserve to be paid.
But Africa is extremely poor and the rest of the world suffers the consequences when we can't be arsed to make their problems solvable at a price point they can afford.
>The incentive would seem to depend only on cost, and any vaccine developer would know that Gilead can likely lower cost at will, making it impossible to recoup vaccine development costs.
This is a good argument that some drugs should be developed by state grants or bounties and the patent is in the state. Something similar delivered covid vaccines in record time - in the form of massive pre purchase agreements.
Vaccines could be cool to give to entire populations, or for really poor or hard to reach places, doing a one and done approach. It could be part of kids’ shot regiment that they don’t even think about, like the hpv vaccine now.
Then for moderate and high risk people they could do the twice yearly shot once it becomes relevant.
I’m no expert in this field at all, just doing my armchair analysis here.
All 55 of those infections were observed in trial participants randomised to the tenofovir/emtracitabine groups. There were no infections in the lenacapavir group.
The site also indicated that "Adherence to F/TAF and F/TDF was low" which means those that got infected most likely weren't taking their pills on a daily basis, unfortunately.
It's not hard to find groups of society where expose to HIV is very high, which are the ideal groups to study. Many people in these groups see contracting HIV as inevitable and do not fear it as you would expect, as it is not seen as a shame or death as as it was around the late 80s.
There subculture of people are people who actively try to transmit / contract HIV, often at so called "biohazard parties".
So I won't tell you to keep reading like others (which you should), but these studies don't work by some research scientist having an HIV+ blood IV at the ready with some "you might notice a little prick" trope, they offer these medications to people that are already in high-risk groups and are conducting activities that make them the most likely demographic to obtain or transmit HIV. Folks like promiscuous homosexuals, prostitutes, drug addicts (risk of sharing needles), and focus groups like that.
I think this study was just young African women in a high incidence area. They basically picked the most likely place in the world a person would get it
I've spent plenty of time around the majority of devs, and I can assure you they don't kiss, lick, suck or fuck anything besides the empty Pringles can.
My sympathies for your situation - it's difficult to have to see such terrible diseases take away those we love.
That being said, are all individuals in a position to take preventative measures against HIV? And does research of a disease (and ways to treat it) only benefit development of drugs that treat that disease?
This is a very US-centric view. Further, it could be applied all the way down the rabbit-hole. "My brother has MS, and my sister is a few years from a diagnosis. It's nice to know money is being spent on dementia treatments, a disease that almost exclusively affects the elderly already near end-of-life, when that money could be going toward researching cures for diseases affecting people with much more of their lives to live."
Effective altruism sounds nice and fuzzy, but it's pretty silly in practice. It's also not like we can just point all scientists and scientific organizations toward a few of the most highly problematic diseases. At best, there'd be an enormous amount of resources wasted on duplication of efforts.
> "My brother has MS, and my sister is a few years from a diagnosis. It's nice to know money is being spent on dementia treatments, a disease that almost exclusively affects the elderly already near end-of-life, when that money could be going toward researching cures for diseases affecting people with much more of their lives to live."
Sounds reasonable.
> At best, there'd be an enormous amount of resources wasted on duplication of efforts.
There's always the risk of losing previously effective drugs due to resistance, so the value of redundancy cannot be overstated