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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 ye

by hodder 2y ago

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?

deleted 2y ago
[deleted]
4fterd4rk 2y ago
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 2y ago
  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 2y ago
    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 2y ago
      What about with coronaviruses?
      - fwip 2y ago
        SARS was caused by a coronavirus.
      - nkozyra 2y ago
        Fair argument for doing it with highly mutative viruses like coronavirus and influenza, because it gives you a chance to prepare.
        mkolodny 2y ago
        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 2y ago
        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 2y ago
        “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-vaccine-design.html https://nymag.com/intelligencer/2020/12/moderna-covid-19-vac...
  - Moldoteck 2y ago
    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 2y ago
    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 2y ago
      [dead]
- shellfishgene 2y ago
  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 2y ago
> 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 2y ago
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 2y ago
  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 2y ago
(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 2y ago
  Are you an elcor?
- Vecr 2y ago
  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 2y ago
    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 2y ago
      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 2y ago
        reverts as in becomes an acute polio case
- foobiekr 2y ago
  I know it was a joke but lots of bacteria can survive simple boiling as endospores.

by hodder 2y ago

deleted 2y ago

[deleted]

4fterd4rk 2y ago

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 2y ago
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 2y ago
  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 2y ago
    What about with coronaviruses?
    - fwip 2y ago
      SARS was caused by a coronavirus.
    - nkozyra 2y ago
      Fair argument for doing it with highly mutative viruses like coronavirus and influenza, because it gives you a chance to prepare.
      - mkolodny 2y ago
        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 2y ago
        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 2y ago
        “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-vaccine-design.html https://nymag.com/intelligencer/2020/12/moderna-covid-19-vac...
- Moldoteck 2y ago
  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 2y ago
  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 2y ago
    [dead]
shellfishgene 2y ago
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 2y ago

> 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 2y ago

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 2y ago
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 2y ago

(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 2y ago
Are you an elcor?
Vecr 2y ago
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 2y ago
  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 2y ago
    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 2y ago
      reverts as in becomes an acute polio case
foobiekr 2y ago
I know it was a joke but lots of bacteria can survive simple boiling as endospores.