One other very cool thing here is that this new treatment represents a whole new family of drugs (very sophisticated at that, per Derek Lowe's assessment). I thought back in the late 2010s with integrase inhibitors (e.g. dolutegravir), there was a real chance they could achieve the 90-95% reduction targets in new cases, and hopefully this new drug makes that even more feasible.
There's always the risk of losing previously effective drugs due to resistance, so the value of redundancy cannot be overstated
Not my field so please bear with me. Before watching the video
the notion of interfering with the capsid as a mechanism for stopping the virus made sense.
However, what I still don't have a handle on is how does lenacapavir act so long that it only needs to be administered every six months?
From the explanation lenacapavir works on the capsid directly, it's not acting on the immune system by training the body's defences as with a traditional vaccine. Surely this molecule can't just hang around for six months without being gobbled up by the liver or such.
>There's always the risk of losing previously effective drugs due to resistance, so the value of redundancy cannot be overstated
Redundancy in HIV drugs is extremely important and significantly more resources should be applied to such drugs, as well as to treatment regimens and vaccines that can significantly reduce HIV infection and the horrible effects of AIDS.
In fact, we've made enormous advances over the past 35+ years. My (late) sister's (late) husband was a hemophiliac and, like most American hemophiliacs[0], was infected with HIV because big pharma refused to test the blood products[1] they were selling to hemophiliacs, even though they knew there was a significant risk in doing so.
In any case, my sister took care of her husband for nearly 15 years, until he finally died a slow, painful death in 1996. My sister was also HIV+ and didn't wish to suffer the way her husband had, especially since there was no one to care for her the way she cared for him. And so, over Memorial Day weekend, 1996, my sister took her own life rather than die a slow, painful death.
The irony, of course, was that the first protease inhibitors were approved by the FDA five or six months later. Had she waited, she might well be alive today. And more's the pity.
As such, I strongly believe in research to prevent, treat and cure HIV/AIDS, and heartily agree that we need more good drugs and treatments.
However, the value of anything can be overstated, including redundancy in HIV drugs.
"Without significant redundancy in HIV drugs, all life in the universe will be extinguished."
"Without significant redundancy in HIV drugs, our sun will explode in 2043."
"Without significant redundancy in HIV drugs, the oceans will boil, then evaporate in the next six weeks."
I could go on, but I presume you get the idea.
Hyperbole can be a short-term motivator, but we need to continue over the long term to stop HIV/AIDS. So, please do advocate for more research/drugs/treatments, but please don't use such language in doing so -- it cheapens the argument and potentially reduces the resources available for the efforts you clearly want.
Feel free to disagree, but doing so will give you terminal cancer.[2]
> Hyperbole can be a short-term motivator, but we need to continue over the long term to stop HIV/AIDS.
I am expecting the findings of this trial to be regurgitated by the general population who refer to the science community. “THEY cured AIDS” will be declared without the nuance of “well, new infections are prevented with a biannual depot injection …”
> Redundancy in HIV drugs is extremely important and significantly more resources should be applied to such drugs
Does HIV prevention research get more resources than curing cancer? I'm looking through the NIH website and asking Claude and so far the evidence I've seen is leading me to believe that's true, but I could be mistaken.
I wonder how much this will cost? A drug you take 2 times a year could be much cheaper than one you take 365 times a year, and that's a big deal.
The existing daily pill is really expensive. Australia knew that PrEP would practically eliminate HIV transmission. Even so, the decision to pay for it took years and was fiercely contested. That was before COVID, and people are more willing to pay for public health today. But cheap PReP would make a big difference in the poor countries where HIV prevention really matters.
The shot will likely be exorbitant in the USA. Gilead charged almost $2k/month for Truvada (list price, of course) and Descovy is the same. Generic Truvada is like $30/month now, so the price was never about the cost to manufacture. Obviously Gilead is developing these new drugs/shots for when Descovy's patent expires.
They rely on the government mandating that health insurance companies cover the shots. This drives up the price.
The price is rarely ever about the manufacturing cost.
"A new study in 2020 estimated that the median cost of getting a new drug into the market was $985 million, and the average cost was $1.3 billion, which was much lower compared to previous studies, which have placed the average cost of drug development as $2.8 billion.[4]"
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.
I'm no fan of pharma industry but there's an unfounded and troubling assumption embedded in this comment: that any drug price over cost-to-manufacture can only be extortion. How do people recoup R&D costs (which are the vast majority of costs in getting a new drug onto the market)?
The 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.
In the Netherlands until recently you could get it for ~$10/mo (now ~$20). We have a whole website naming prices in different pharmacies around the country.
Like the other commenters allude to, how would you like software mandated to cost just 10% margin over COGS? Do you think selling cloud services for 10% more than the cost of server parts is going to be a business when there's thousands of software engineers in R&D needed?
If it's like every other IP-encumbered drug, the price will be approximately "the value the recipient places on HIV resistance," which is probably close to what's being charged now.
Why would they give up the profit? What's your rationale here?
Cure = $X
If the treatment is daily then it's $X/365 if it's monthly the price is $X/12 if it's twice a year it's $X/2
Imagine being an exec at that company and being like "let's give up 50/52 of our profit because it's more convenient for the patient"? How many hours would it take between giving that speech and getting fired, do you think?
Please forgive my lack of understanding. This appears to be a great achievement.
Is there any risk that a Lenacapavir resistant strain would rise up in many years as a result of treating a large portion of the global at risk population (estimated to be 60m people receiving the injection to materially lower global HIV rates)?
Sort of like how antibiotic resistant bacteria rates seems to evolve out of the use of antibiotics? Or is that not a thing and Im just clueless?
"The medication works in two ways: First, it interrupts viral replication by preventing HIV from reaching the nucleus of an infected cell, which then blocks reproduction.
The second mechanism is for cases in which integration of the HIV genome has already occurred. In this instance, lenacapavir interferes with production of viral progeny, “making them defective so that they are not able to infect other cells.” Therefore, it works in both early and late stages of the HIV life cycle to disrupt replication."
Since the drug works in two ways, it would be difficult for the virus to adapt. Similarly to how the current commonly prescribed PrEP regimen (Descovy or Truvada) is two different drugs in one pill and has not lead to any significant rise in resistance.
> Please forgive my lack of understanding. This appears to be a great achievement. Is there any risk that a Lenacapavir resistant strain would rise up in many years as a result of treating a large portion of the global at risk population (estimated to be 60m people receiving the injection to materially lower global HIV rates)?
Not really. This same principle has been used for over a decade. The only difference here is that the previous version of injectables needed to be administered every two months, whereas this can be done every six months.
HIV drug resistance is a real issue, not sure why other comments are dismissing the risk of resistance. The risk of resistance is why HIV positive individuals take a cocktail of drugs, and why PrEP (Truvada or Descovy) requires regular HIV testing (because if you end up positive you need to upgraded to a cocktail of drugs).
PrEP is incredibly effective, and even better than condoms at preventing HIV. There's various reasons it requires regular testing:
- While very effective, it requires people to actually take it consistently, which is why the injectable form is better for some than the pill.
- PrEP is not without side effects for a small portion of its users. In some cases it can cause bone density loss, or kidney damage. These tests are intended to catch any issues before they cause any permanent damage.
- Since people are coming in to get tested for the aforementioned issues, they also run a full STI panel. This is great and it means those on PrEP (And those managing HIV) are tested more frequently than the general population, and are less likely to transmit an STI than those who don't come in for regular testing.
(Joke) I'm still waiting for bacteria to evolve a resistance to boiling!
(Seriousness) Different infectious agents can / can not evolve around their vaccines. We don't get yearly polio shots, we do get yearly covid/flu shots.
(Speculation) It's probably too early to tell if there's a way for HIV to evolve around this, but it might have something to do with how effective we are at killing HIV in our population to begin with.
Polio can and does mutate almost instantly around the vaccines, but since some of the vaccines are live polio anyway people don't really care. "Mutation" is not really a word that matters, what matters is if a variant is causing problems.
Without mention of the number of study participants or risk, I was a bit suspicious, but it's not a tiny sample size, and not a low-risk group. From the paper:
> Among 5338 participants who were initially HIV-negative, 55 incident HIV infections were observed: 0 infections among 2134 participants in the lenacapavir group
The infections in the control groups were in people taking other preventative medication, not nothing.
In terms of protecting oneself, what are the actual steps? (E.g. if you're HIV- but are participating in activities either directly with someone who is HIV+ or whose partner is HIV+.)
Do you schedule a doctor appointment and ask for something specific? And is there anything else to do, such as something over-the-counter?
There's a dizzying array of terms to learn in this space. PrEP is apparently different from PEP, which I think is also unrelated to what this article is talking about. It'd be nice if someone put together a 2024 guide for what the latest preventative / protection mechanisms are.
Assuming you do not currently have a viral load of HIV, you can meet with your provider, indicate that you are at risk, and request a prescription for PrEP [1] (Planned Parenthood can assist with sourcing if you don't have a PCP or other stable medical providers). Longer term, it is likely there will be a shift to a twice yearly injectable (Gilead’s Lenacapavir) [2]. State of the art is an undetectable viral load due to antiviral treatment means you cannot transmit to others [3] [4] [5].
Not medical advice, educational purposes only. Seek a medical professional's guidance for your personal circumstances.
> Longer term, it is likely there will be a shift to a twice yearly injectable (Gilead’s Lenacapavir)
That's debatable. Injectable PrEP has been around for years already (Lencapavir is not the first, just the most recent). Lencapavir has also not yet been tested on all at-risk groups, so unlike other forms of PrEP, it's not a universal solution because it cannot be prescribed to all candidates.
Given the price, which is quite high even with the programs Gilead has said that it will issue to reduce the cost, it remains to be seen how widely-used Lencapavir becomes outside of specific markets.
> 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.
PEP means "post-exposure prophylaxis"; PrEP means "pre-exposure prophylaxis". You take PrEP regularly (if you know you're at risk due to sexual habits etc whatever), but only take PEP in response to a specific possible-exposure event (and not already on PrEP). You want pre-exposure instead of post-exposure because post-exposure is very hard on your body and makes you feel sick.
Clinics are pretty good. But in general, if you’re a woman in a first world nation your odds of getting it are really low, unless you do significant amounts of anal sex with bisexual men or inject drugs.
Same thing with men. Straight men aren’t at much risk. Bi and gay men are at high risk.
If you have a hiv+ partner, prep is good enough to keep you safe. Just take it always as prescribed.
Pep in for when you may have been exposed, and you need to get it as soon as possible. It’s like a morning after pill. Within 72 hours of exposure but sooner is better.
Then for anyone who does unprotected casual sex, there’s doxypep which reduces likelihood of bacterial stds by a lot, so gonorrhea, chlamydia, and syphilis.
If you want a person to explain this to you in real life, there’s different clinics in every American city that would love to take the time to teach you about all of this. Part of their funding is to educate
PrEP - An HIV negative person taking Truvada or Descovy once a day to prevent HIV infection.
PEP - An HIV negative person taking a course of antiretrovirals within 72 hours after exposure to HIV to prevent HIV infection.
This article is referring to injectable PrEP. This is already available via an injection every two months and is typically used in populations that can't be expected to take a pill every day (drug addicts, etc.). The article is referring to a new form of injectable PrEP that extends this to once every six months.
> This is already available via an injection every two months and is typically used in populations that can't be expected to take a pill every day (drug addicts, etc.).
That is a pretty bold parenthetical statement. Not only is it not true that "drug addicts" can't be expected to take a pill every day, but neither cabotegravir nor lenacapavir are tested or approved for HIV acquired through non-sexual means, which makes them a poor choice for PrEP for "drug addicts" compared to oral forms, which are effective against all forms of HIV transmission.
Source: former counselor and educator for HIV and substance use
What I have noticed is that in most situations saying "PrEP" is enough. For my doctor that meant discussing Truvada, Descovy, and what is just kinda dubbed "Injectable Prep". This aligns with most apps also just saying "on prep" with no distinguishing between what prep.
I would imagine that if/when this comes to market it would likely similarly fall under "Prep" for the general community and then you discuss the specifics with your doctor.
Edit: There is also Doxypep (I just say Doxy), which while related to STD's is not related to HIV.
There are people announcing their PrEP status on dating apps so they can raw dog with strangers? Have people forgotten that there are plenty of STD besides HIV?
I think this is highly problematic and lifestyle PrEP seems to be counterproductive as a public health measure.
But I am open to arguments that I’m wrong. It’s possible that I am biased as a monogamous heterosexual who has grown up in a culture where sex without condom, especially outside committed relationships, is generally frowned upon and 1980-1990s HIV scares are still in the consciousness of people.
"Lenacapavir works by binding directly to the interface between HIV-1 viral capsid protein (p24) subunits in capsid hexamers, interfering with essential steps of viral replication, including capsid-mediated nuclear uptake of HIV-1 proviral DNA, virus assembly and release, production of capsid protein subunits, and capsid core formation[1]... It functions by binding to the hydrophobic pocket formed by two neighboring protein subunits in the capsid shell. This bond stabilizes the capsid structure and inhibits the functional disassembly of the capsid in infected cells.[2]"
In other words, it prevents the virus' protein shell (capsid) from being built properly, which in turn prevents the virus from properly opening ("uncoating") once it enters a host cell.
> It functions by binding to the hydrophobic pocket formed by two neighboring protein subunits in the capsid shell
That's entirely cool to me, it operates by exploiting an "incidental construction feature" of the capsid and not targeting any specific feature in and of itself?
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).
Readit News
There's always the risk of losing previously effective drugs due to resistance, so the value of redundancy cannot be overstated
https://www.youtube.com/watch?v=9IbzMbfEMIY
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?
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?
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 …”
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.
Dead Comment
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.
They rely on the government mandating that health insurance companies cover the shots. This drives up the price.
"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
Health insurances in the US mostly only cover Truvada. Some cover Descovy but not many.
https://prepnu.nl/users/price-list/
Dosing doesn't impact price. Pharmaceuticals aren't based on "cost-plus" pricing.
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?
If history is any guide, as much as it possibly can. Probably more.
Sort of like how antibiotic resistant bacteria rates seems to evolve out of the use of antibiotics? Or is that not a thing and Im just clueless?
"The medication works in two ways: First, it interrupts viral replication by preventing HIV from reaching the nucleus of an infected cell, which then blocks reproduction.
The second mechanism is for cases in which integration of the HIV genome has already occurred. In this instance, lenacapavir interferes with production of viral progeny, “making them defective so that they are not able to infect other cells.” Therefore, it works in both early and late stages of the HIV life cycle to disrupt replication."
Since the drug works in two ways, it would be difficult for the virus to adapt. Similarly to how the current commonly prescribed PrEP regimen (Descovy or Truvada) is two different drugs in one pill and has not lead to any significant rise in resistance.
Hopefully not, but evolution is a powerful beast.
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.
- 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.
Deleted Comment
(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.
Dead Comment
> 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.
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.
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...
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.
> 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?
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
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.
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
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.
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.
Dead Comment
How does it actually do it?
"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
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?
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...
Deleted Comment
https://www.science.org/content/blog-post/things-i-won-t-wor...