[HN Gopher] Prevention of HIV
___________________________________________________________________
Prevention of HIV
Author : etiam
Score : 621 points
Date : 2024-08-07 19:11 UTC (1 days ago)
(HTM) web link (www.science.org)
(TXT) w3m dump (www.science.org)
| sillysaurusx wrote:
| 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.
| toomuchtodo wrote:
| 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.
|
| [1] https://www.hiv.gov/hiv-basics/hiv-prevention/using-hiv-
| medi...
|
| [2] https://news.ycombinator.com/item?id=40742163
|
| [3] https://www.hiv.gov/hiv-basics/staying-in-hiv-care/hiv-
| treat...
|
| [4] https://www.niaid.nih.gov/diseases-conditions/treatment-
| prev...
|
| [5] https://www.hiv.gov/blog/science-validates-undetectable-
| untr...
| ClarityJones wrote:
| From [5] https://www.hiv.gov/blog/science-validates-
| undetectable-untr...:
|
| > 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.
|
| What? Isn't that the primary transmission vector?
| toomuchtodo wrote:
| From that same link you cite:
|
| > 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.
|
| https://www.nih.gov/news-events/news-releases/hiv-control-
| th...
|
| https://web.archive.org/web/20150106032855/http://www.niaid
| ....
|
| https://www.clinicaltrials.gov/study/NCT00074581
| pstrateman wrote:
| >1,600 heterosexual couples
|
| Is there a similar study of gay men who are not in a
| monogamous relationship?
|
| Studying the group with the lowest transmission rate who
| could still transmit seems kind of dishonest.
| foldr wrote:
| It's not 'dishonest'. It's important data for parts of
| the world where heterosexual transmission of the virus is
| common.
|
| And yes, there is a similar study: https://www.thelancet.
| com/journals/lancet/article/PIIS0140-6...
| Vecr wrote:
| 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.
| 4fterd4rk wrote:
| This has been extensively studied and you are wrong.
|
| https://www.thelancet.com/journals/lancet/article/PIIS014
| 0-6...
| Vecr wrote:
| 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.
| theideaofcoffee wrote:
| 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).
| Vecr wrote:
| 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).
| serf wrote:
| >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.
| foldr wrote:
| 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.
| Vecr wrote:
| 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.
| foldr wrote:
| Why don't you ask one and post what they say here? Or
| better still, post a reference to some published work
| that makes your point.
| hyrix wrote:
| 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
|
| https://www.idsociety.org/science-speaks-blog/2021/u--
| u-the-...
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8942556/
| dyauspitr wrote:
| From what I've read you need an absolute minimum of 10
| virons for infection to happen.
| etiam wrote:
| 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.
|
| https://journals.plos.org/plosbiology/article?id=10.1371/
| jou...
|
| 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.
| chimeracoder wrote:
| > 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.
| borski wrote:
| 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?
| chimeracoder wrote:
| > 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.
| borski wrote:
| 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.
|
| But I tend to be an optimist.
| nerdjon wrote:
| 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.
| chimeracoder wrote:
| > 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.
| argonaut wrote:
| 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.
| nerdjon wrote:
| 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.
| chimeracoder wrote:
| 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).
| chimeracoder wrote:
| > 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.
| argonaut wrote:
| You are right, my comment is only valid in California.
| FireBeyond wrote:
| 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.
|
| Hmm.
| nerdjon wrote:
| 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.
| felixg3 wrote:
| 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.
| iknowstuff wrote:
| 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.
| theideaofcoffee wrote:
| 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.
| felixg3 wrote:
| 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 naivete
| and not malice.
| scotty79 wrote:
| Great list. Although suddenly sex when single seems like
| even more of a bother than before.
| iwontberude wrote:
| HSV is inevitable if you hookup, but its also not that
| bad.
| switch007 wrote:
| They know other STDs exist but thanks for the insinuation
| that all homosexuals - sorry - "people" are stupid
| consteval wrote:
| > 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.
| 4fterd4rk wrote:
| 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.
| chimeracoder wrote:
| > 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
| fragmede wrote:
| > Not only is it not true that "drug addicts" can't be
| expected to take a pill every day,
|
| The general population can't be expected to take a pill
| every day, what would make anyone believe people with SUD
| are able to?
|
| Source: person who's expected to take a pill every day, and
| knows other people who are supposed to taste a pill every
| day.
| chimeracoder wrote:
| > 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.
|
| Source: clinical data and professional experience
| curiousthought wrote:
| Adherence to a single tablet regimen is significantly
| higher than a multi tablet regimen. Bringing some actual
| data into this, adherence to either in a broad population
| is not 100%: https://www.ncbi.nlm.nih.gov/pmc/articles/PM
| C5253105/#:~:tex....
|
| 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.
| 4fterd4rk wrote:
| 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.
| masspro wrote:
| 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.
| dyauspitr wrote:
| Why is post exposure so hard on the body. Isn't it still just
| a 2 drug cocktail (truvada+another one)?
| Eumenes wrote:
| Don't have sex with strangers you don't trust.
| barfingclouds wrote:
| 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
| pfdietz wrote:
| It's a wonderful (if rare) event when a medical trial is stopped
| for efficacy.
| hodder wrote:
| 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?
| 4fterd4rk wrote:
| From another source:
|
| "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.
| gibolt wrote:
| Difficult doesn't mean impossible. Trillions and trillions of
| chances for mutations to happen may lead to resistance over
| some period of time.
|
| Hopefully not, but evolution is a powerful beast.
| Vecr wrote:
| 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.
| ljsprague wrote:
| What about with coronaviruses?
| fwip wrote:
| SARS was caused by a coronavirus.
| nkozyra wrote:
| Fair argument for doing it with highly mutative viruses
| like coronavirus and influenza, because it gives you a
| chance to prepare.
| mkolodny wrote:
| 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.
| HaZeust wrote:
| Can you please cite a source that shares that it took
| "less than a week" for the COVID vaccine to be developed
| after discovery?
| mkolodny wrote:
| "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"
|
| https://nymag.com/intelligencer/2020/12/moderna-
| covid-19-vac...
| palata wrote:
| 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.
| zelphirkalt wrote:
| Is this assuming, that Covid was lab made? Since I have
| not seen or read about proof of that theory, this comes
| across a bit like conspiracy theory.
| jjeaff wrote:
| 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.
| andai wrote:
| 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.
|
| https://en.wikipedia.org/wiki/List_of_laboratory_biosecur
| ity...
|
| 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...
| -\\_(tsu)_/-
|
| Source: a study by the US senate, covered here by WSJ:
| https://archive.ph/Kh2Fr
| nemo44x wrote:
| 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.
| Moldoteck wrote:
| 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
| est31 wrote:
| 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.
| cchi_co wrote:
| Its persistent nature requires extensive resources and
| continuous monitoring. this virus reminds me Loki from
| Norse mythology
| shellfishgene wrote:
| As far as I understand it both ways are based on the drug
| binding to the capsid, so if the capsid protein changed
| resistance could evolve.
| chimeracoder wrote:
| > 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.
| argonaut wrote:
| 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).
| ProfessorLayton wrote:
| 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.
| gwbas1c wrote:
| (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.
| shrimp_emoji wrote:
| Are you an elcor?
| Vecr wrote:
| 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.
| foobiekr wrote:
| 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.
| Vecr wrote:
| 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.
| foobiekr wrote:
| reverts as in becomes an acute polio case
| foobiekr wrote:
| I know it was a joke but lots of bacteria can survive simple
| boiling as endospores.
| thisrod wrote:
| 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.
| argonaut wrote:
| 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.
| ortusdux wrote:
| 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]"
|
| https://en.wikipedia.org/wiki/Cost_of_drug_development
| chimeracoder wrote:
| > "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.
| HideousKojima wrote:
| 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).
| roughly wrote:
| 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.
| pfdietz wrote:
| 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.
| Jensson wrote:
| > 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.
| Nifty3929 wrote:
| "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.
| Jensson wrote:
| > The pharma industry COULD do their own foundational
| research, but the university system cannot bring a drug
| to market.
|
| You can't use an "in theory" argument for one side but
| not the other.
|
| In theory governments could bring medicine to market, in
| practice they don't/can't.
|
| In theory pharma industry could do foundational research,
| but in practice they don't/can't.
| FireBeyond wrote:
| If there's no pharma industry?
|
| You act like the solution would be "oh well, no meds for
| anyone then!" and not "let's expand university programs
| to meet that need".
| ClumsyPilot wrote:
| > 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?
| robotresearcher wrote:
| Pharma companies are chock full of PhD types, as are the
| tech companies and Wall Street.
|
| What companies don't have is PhD _students_. They are
| numerous, smart, very cheap, and work very hard.
| a-dub wrote:
| 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.
| mensetmanusman wrote:
| That's also like any endeavor with tech.
| wdwvt1 wrote:
| 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.
|
| [0]
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10812233/
| [1] https://www.science.org/content/blog-post/where-
| drugs-come-n... [2]
| https://www.fiercebiotech.com/research/report-industry-
| not-n... [3] https://www.nih.gov/about-nih/what-we-
| do/budget
| Symmetry wrote:
| The usual story is that academia finds an interesting
| mechanism to produce the desired effect. Though
| occasionally this is done by industry instead.
|
| Then industry turns that into a specific molecule that
| can enter the human body in a standard way and doesn't
| produce too many side effects.
|
| Then industry figures out how to produce that molecule at
| scale reliably in a sufficiently pure form.
|
| And at the same time industry is shepherding the drug
| through clinical trials.
| ortusdux wrote:
| 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.
| chimeracoder wrote:
| > 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.
| pfdietz wrote:
| 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.
| Nifty3929 wrote:
| 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.
| FireBeyond wrote:
| 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".
| pfdietz wrote:
| I understand 60% of drug candidates fail in phase 3, the
| last and most expensive phase of testing.
|
| There are of course lots of chemicals ruled out early,
| but that's before you have something you'd call a drug.
| FireBeyond wrote:
| 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.
| kbolino wrote:
| _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.
| directevolve wrote:
| We do have some shaky and hard to interpret data.
|
| 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.
|
| [1] https://www.sciencedirect.com/science/article/pii/S01
| 6885101... [2]
| https://www.nature.com/articles/nrd.2017.70.pdf [3]
| https://pubmed.ncbi.nlm.nih.gov/26908540/ [4]
| https://www.cbo.gov/publication/57126
| FireBeyond wrote:
| > 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.
| FireBeyond wrote:
| 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...
| pfdietz wrote:
| 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.
| tbrownaw wrote:
| > _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).
| JoelEinbinder wrote:
| I'm not going to invest a drug company with a 90% chance
| of failure unless I can expect to get a 10x return if it
| succeeds.
| FireBeyond wrote:
| 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".
| refurb wrote:
| Clinical trial failure rates (or inversely success rates)
| have been analyzed before.
|
| https://www.nature.com/articles/nrd.2016.136
|
| _" 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.
| FireBeyond wrote:
| 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.
| refurb wrote:
| Right, but with the cost distribution for clinical
| trials, costs increase by 4x in phase 2, then 8x in phase
| 3 (relative to phase 1).
|
| So despite attrition that reduces candidates by 9x by
| phase 3, costs have increased by 8x.
|
| [1]https://www.sofpromed.com/how-much-does-a-clinical-
| trial-cos...
| mlyle wrote:
| 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.
| pfdietz wrote:
| 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.
| mlyle wrote:
| That's close to what I tried to say.
|
| 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.
| hanniabu wrote:
| Also the government, aka the public, subsidizes a lot of
| those costs
| rishav_sharan wrote:
| Talking of studies, from the same wiki 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]
| mortehu wrote:
| 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.
| gomox wrote:
| These original $3B numbers are highly misleading, to the
| extent that I deem them to be bordering on a straight up
| lie.
|
| See: https://news.ycombinator.com/item?id=18693177
| Analemma_ wrote:
| 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)?
| asveikau wrote:
| Doesn't the government also fund a lot of pharma R&D?
|
| Here's a 2019 article that came up in a Google search:
| Taxpayers funded this HIV research. The government patented
| it. Now a company profits
| https://www.latimes.com/business/la-fi-gilead-sciences-
| truva...
| tptacek wrote:
| Taxpayers fund all sorts of stuff that is ultimately
| commercialized!
| kiba wrote:
| 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.
| asveikau wrote:
| So that's an argument that the government and the public
| should get a return on that investment, or profits should
| be constrained.
|
| Or an argument against exclusive rights being in private
| hands.
| sroussey wrote:
| Universities certainly do. IP transfer is big business.
|
| Subsidies for oil, not so much.
| ToValueFunfetti wrote:
| 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
| asveikau wrote:
| 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.
| ToValueFunfetti wrote:
| 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.
| asveikau wrote:
| 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.
| tptacek wrote:
| 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.
| asveikau wrote:
| > 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.
| ToValueFunfetti wrote:
| 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.
| heavyset_go wrote:
| > _The public gets access_
|
| Just a reminder that on-patent Truvada cost $4,500 for a
| 30 day supply of a drug that needs to be taken every day.
| BigJono wrote:
| What do you mean by "gets access"?
|
| 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.
| pfisherman wrote:
| 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.
| chimeracoder wrote:
| 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.
|
| PrEP has been pure, risk-free profit for Gilead.
| yieldcrv wrote:
| Although this is a discussion about costs
|
| 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
| jayshua wrote:
| Gilead claims that is false and that they spent 1.1
| billion on developing Truvada.
| https://www.gilead.com/news-and-press/company-
| statements/gil...
| comex wrote:
| 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.
| chimeracoder wrote:
| > 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.
| chimeracoder wrote:
| > Gilead claims that is false and that they spent 1.1
| billion on developing Truvada.
| https://www.gilead.com/news-and-press/company-
| statements/gil...
|
| 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.
| WalterSear wrote:
| > 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.
|
| https://www.bu.edu/sph/files/2015/05/Pharmaceutical-
| Marketin...
| AuryGlenz wrote:
| Marketing gets them more money, which then increases the
| amount they can put into R&D. They aren't spending on
| marketing without expecting a return.
| sethammons wrote:
| They shouldn't make tv ads; they should be in a white
| paper that doctors read.
| WalterSear wrote:
| R&D is still not where the vast majority of their money
| is spent.
| smt88 wrote:
| 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.
| scotty79 wrote:
| 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.
| mock-possum wrote:
| 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.
| reducesuffering wrote:
| 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?
| LeifCarrotson wrote:
| 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.
| vasco wrote:
| 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.
|
| In fact, it still costs $750 today.
| pdntspa wrote:
| That would be amazing! More businesses need a costs-plus
| gun held to their head.
| renewiltord wrote:
| 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.
| pdntspa wrote:
| Businesses are not people (despite what the law tries to
| make you think), and people should not be bound by the
| same limits as businesses.
| renewiltord wrote:
| 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.
| pdntspa wrote:
| 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.
| sethammons wrote:
| 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
| refurb wrote:
| Would you be willing to work for a cost-plus salary?
|
| Figure out what a middle-class lifestyle costs and pay
| you 10% more?
| amrocha wrote:
| You're saying this ironically but yes, I would. If there
| was an accepted living standard and every job paid
| according to that that would be amazing.
| refurb wrote:
| That seems very anti-worker.
| amrocha wrote:
| Only if you're in the minority that makes more than they
| should
| malfist wrote:
| No one is suggesting it should be billed at only the cost
| of manufacturing. Recouping expenses incurred during R&D
| are perfectly reasonable.
|
| If you poked at the data a bit, you might find it
| interesting to learn that drug companies spend more money
| on advertising than R&D
| bobthepanda wrote:
| There is a two-month shot now (Apretude) and I was quoted $4K
| a shot when I asked about it.
|
| Health insurances in the US mostly only cover Truvada. Some
| cover Descovy but not many.
| renewiltord wrote:
| 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.
| Cthulhu_ wrote:
| Are you insinuating that the only expense the company
| behind intellij has is the data transfer?
| namdnay wrote:
| It was clearly sarcastic
| consteval wrote:
| The difference here is that:
|
| 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.
| isoprophlex wrote:
| Crony capitalism at its best.
| modeless wrote:
| 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.
| vasco wrote:
| 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.
| amrocha wrote:
| 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.
| vasco wrote:
| 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?
|
| Look, random example
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10370755/ -
| explain why if they are not motivated by profit, how is
| it possible that the outcome of this paper happens?
|
| 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.
| amrocha wrote:
| 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.
| modeless wrote:
| 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!
| amrocha wrote:
| 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?
| modeless wrote:
| 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.)
| amrocha wrote:
| 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.
| modeless wrote:
| 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.
| tirant wrote:
| I don't know of any researcher not working for profit,
| none. Not only that, I would always want them to earn as
| much as possible, if they deserve it.
| amrocha wrote:
| Researchers aren't the ones profiting off of price
| gouging.
|
| Of course they're working for money, they live in
| society.
| paulmist wrote:
| 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.
|
| https://prepnu.nl/users/price-list/
| barfingclouds wrote:
| Well we have a hiv prep shot already that's every two months.
| I forgot the name, but yeah I think it's very expensive
| refurb wrote:
| > 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.
|
| Dosing doesn't impact price. Pharmaceuticals aren't based on
| "cost-plus" pricing.
| hadlock wrote:
| 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?
| barryrandall wrote:
| 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.
| michaelcampbell wrote:
| > I wonder how much this will cost?
|
| If history is any guide, as much as it possibly can. Probably
| more.
| w10-1 wrote:
| 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.
| ReptileMan wrote:
| >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.
| KoolKat23 wrote:
| It will be virtually non-existent in Africa if it is priced
| like that.
| dyauspitr wrote:
| It will be non existent in Africa until India starts making
| the generics. That's how it has historically been for most
| prescription medication there.
| DoreenMichele wrote:
| 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.
| barfingclouds wrote:
| 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.
| inasio wrote:
| 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
| w10-1 wrote:
| Here's a summary including the mechanism of action from a UW
| professor in 2022:
|
| https://www.youtube.com/watch?v=9IbzMbfEMIY
| hilbert42 wrote:
| 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.
|
| What am I missing here?
| jaggederest wrote:
| 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.
| hilbert42 wrote:
| 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.
| mensetmanusman wrote:
| The drug is a PFAS (as nearly half of new drugs are), so it
| can act that way in the body.
| FooBarWidget wrote:
| I thought PFAS are toxic?
| amarant wrote:
| 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.
| vasco wrote:
| 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.
| PetitPrince wrote:
| 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).
|
| Also, the dose makes the poison, etc.
| Twisol wrote:
| > It's like saying "I though canine were dangerous?" (yes
| for big cats, no so much for your average French
| bulldog).
|
| Big cats are not canines :(
| mangamadaiyan wrote:
| Cats, big as well as small, are feline :)
| PetitPrince wrote:
| Ah sorry, my French bias is shining through. I meant
| "canine tooth" (also known as a fang), not the _Canis_
| genus.
| Twisol wrote:
| Ah, that totally makes sense! No worries :)
| mensetmanusman wrote:
| 'PFAS toxic' is about as sophisticated as saying 'Nuclear
| bad'.
|
| Western society isn't scientifically literate enough to
| develop these things at the moment, so they will happen
| in APEC for now.
| refurb wrote:
| > 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.
| 14 wrote:
| 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.
| supertofu wrote:
| For someone with bone loss, isn't the long half life a
| good thing?
| suchire wrote:
| 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:
|
| https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.3c00626
|
| 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.
| rlad wrote:
| No problem with this is it it does not interfere with
| infection. Only with replication. So it will not stop people
| from becoming infected.
| sddsdd wrote:
| 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".
| scotty79 wrote:
| There's no infection without replication.
| sixfiveotwo wrote:
| 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.
| oasisaimlessly wrote:
| Epithelial skin / mucosa cells are the most likely
| "patient zero" cells, and those are shed regularly.
| sfn42 wrote:
| Infection is when the virus replicates faster than the body
| can eliminate it.
| nobody9999 wrote:
| >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]
|
| [0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917149/
|
| [1] https://www.cbsnews.com/news/bayer-says-it-settled-
| decades-o...
|
| [2] See what I did there?
| cossatot wrote:
| I'm sorry your family was put through so much termoil.
| jart wrote:
| > 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.
| patmorgan23 wrote:
| Maybe? But Cancer isn't a single disease, it's a class of
| diseases, it has a lot more causes and symptoms and
| treatments than HIV.
| nobody9999 wrote:
| >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
| cancer _s_ and other deadly diseases as well.
| xattt wrote:
| > 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 ..."
| cchi_co wrote:
| This mechanism of action is unique among antiretrovirals
| nothrowaways wrote:
| > The medication interrupts viral replication by preventing HIV
| from reaching the nucleus of an infected cell.
|
| How does it actually do it?
| mrtesthah wrote:
| 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)._
|
| 1.
| https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e56...
| tjohns wrote:
| From Wikipedia:
|
| "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.
|
| [1]: https://en.wikipedia.org/wiki/Lenacapavir
|
| [2]: https://en.wikipedia.org/wiki/HIV_capsid_inhibition
| nothrowaways wrote:
| Thought Lenacapavir was just a chemical. If it knows where
| the nucleus is, is Lenacapavir an organism?
| tjohns wrote:
| Yes, Lenacapavir is just a chemical.
|
| 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.
|
| I'd recommend watching this video:
| https://vimeo.com/260291607
|
| See timestamps 1:33 and 2:47.
| akira2501 wrote:
| > 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?
| nothrowaways wrote:
| > Among 5338 participants who were initially HIV-negative, 55
| incident HIV infections were observed...
|
| Wait what? Those 55 got infected during the trial. What was the
| incentive to get exposed?
| matthewmacleod wrote:
| All 55 of those infections were observed in trial participants
| randomised to the tenofovir/emtracitabine groups. There were no
| infections in the lenacapavir group.
| kemitche wrote:
| 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.
| cypherpunks01 wrote:
| Yes, it can be confusing if you only read part of a sentence.
| Recommend continue reading if you're interested in the findings
| HaZeust wrote:
| 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.
| barfingclouds wrote:
| 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
| sureIy wrote:
| HNers need to stop downvoting questions, however "stupid" they
| might sound.
| mjbeswick wrote:
| 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".
| sterlind wrote:
| "biohazard parties" are for HIV+ men only. you don't have to
| fear transmitting HIV if your partners are already HIV+.
| AbortedLaunch wrote:
| Maybe when on treatment, otherwise superinfections are a
| thing and associated with poorer outcomes.
| barfingclouds wrote:
| Just to interject, but I'm a bisexual male and I've never
| once heard of a biohazard party in real life
| barfingclouds wrote:
| They did this study in a high risk group, so that rate of
| infection was expected
| jaymee wrote:
| I hope that vaccines can be made affordable, otherwise, it won't
| solve anything.
| mkl wrote:
| 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.
| happybuy wrote:
| As with all drugs, efficacy is only one part of the equation.
|
| What's the potential side effects, both short term and long term,
| of this treatment?
|
| For this treatment, it may be negligible, but without saying so
| we are only hearing one side of the story.
| hyrix wrote:
| 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.
|
| https://www.niaid.nih.gov/news-events/nih-statement-prelimin...
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10879468/
| breck wrote:
| > 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?
| hyrix wrote:
| 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.
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133138/
| breck wrote:
| 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.
|
| Thanks for the article. Good read!
|
| [0] https://news.ycombinator.com/newsguidelines.html
| dyauspitr wrote:
| 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?
| fzeroracer wrote:
| Historically according to who and what, exactly? Are you
| going to actually supply a citation here?
| iEchoic wrote:
| Derek Lowe is a great writer. Worth reading his "Things I Won't
| Work With" articles if you want to read more of his writing.
|
| https://www.science.org/content/blog-post/things-i-won-t-wor...
| wsc981 wrote:
| 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.
|
| https://www.youtube.com/watch?v=W1FXbxDrDrY
|
| It's a quite old interview (1996), wonder in what ways knowledge
| has changed regarding the disease.
| mercutio2 wrote:
| Kary Mullis's AIDS denial has been very, very thoroughly
| debunked.
|
| I would not recommend listening to him about AIDS.
| devonsolomon wrote:
| 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.
| cchi_co wrote:
| Such news and articles within the framework of medical research
| warm my soul
| hacker_88 wrote:
| Hell yeah..give it to me.. no not really
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