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>An "elite controller" is a person living with HIV who is able to maintain undetectable viral loads for at least 12 months despite not having started antiretrov

>An "elite controller" is a person living with HIV who is able to maintain undetectable viral loads for at least 12 months despite not having started antiretroviral therapy (ART) . Elite controllers are rare: for every two hundred people living with HIV, approximately one may be an elite controller (0.5%). > It is not entirely understood why some patients are able to achieve undetectable viral loads without ART. https://www.aidsmap.com/about-hiv/faq/what-elite-controller https://www.aidsmap.com/about-hiv/faq/what-elite-controller

dillondoyle 5y ago
And undetectable === untransmittable. Just in case people here didn't know.
- hdjjhhvvhga 5y ago
  I didn't know this. Could you explain the reason?
  - baq 5y ago
    No detectable virus means no transmissible virus.
    - Drdrdrq 5y ago
      To reiterate the question, why is that?
      - XzAeRosho 5y ago
        That's the million dollar question
      - JulianMorrison 5y ago
        Detection means there is enough virus physically present in the sample for the detection technology to identify it. Infection requires virus particles to be physically present in transmission vectors (fluids, droplets, etc). There's generally also a dose-response effect where more particles means more chance of evading the immune system well enough to establish replication in the victim. So a lack of anything to detect, means a lack of anything to spread an infection.
        Drdrdrq 5y ago
        Thank you, makes sense!
        _Microft 5y ago
        > So a lack of anything to detect, means a lack of anything to spread an infection. One should add that for that the threshold for detection has to be lower than the threshold for infection. Example: let the detection threshold be 10 particles/ml and the infection threshold be 100 particles/ml (*) -> then undetectable implies that it is very improbable that an infection will take place. (*) This is a very crude description. Think of it like this: Every single virion (virus particle) has a very low probability of causing an infection itself but there is a high number of them and for one them it might just work out (higher viral load -> higher risk of successful infection)
        hdjjhhvvhga 5y ago
        > One should add that for that the threshold for detection has to be lower than the threshold for infection. This statement is logical and makes perfect sense - but it's narrower than the original one.
      - space_fountain 5y ago
        I'm not a biologist and this is based on general knowledge and some quick google searches but: We're quite good at detecting viruses if we really want to. PCR can amplify DNA so much that we can detect even 50 viruses per milliliter of blood. A milliliter seems like actually a lot of blood to get into someone else and your innate immune system is capable of finding and neutralizing small amounts of contagions relatively well even if it's never seen it before. I do suspect this is a statistical impossibility though probably you could somehow get incredibly unlucky, for example in your blood momentarily all the free floating viruses end up in the same bit of blood and that somehow gets into someone else, but I think we can all realize that probability is tiny and in practice I don't think there are any examples of transmission with undetectable levels of HIV.
        et2o 5y ago
        Well put. We can actually detect well below 50 copies/mL in the laboratory setting as well; we don’t go below this to maintain adequate test specificity and sensitivity in the clinical setting.
        space_fountain 5y ago
        Not to put you on the spot but from my cellular bio lab I took it felt like PCR should be capable of detecting literally a single example of the targeted bit of DNA in the sample. Is the problem with detecting below 50 that the sample is too easily contaminated or is it that the primers can spontaneously bind to things they aren't supposed to at a high enough rate to invalidate the results?
        jagger27 5y ago
        > A milliliter seems like actually a lot of blood to get into someone else 1 cm^3 is indeed pretty big. That’s 1,000 little millimetre cubes, and we can detect as few as 50 virions in that space! I will point out though that 1 ml is low for semen (more like 2.5 ml or more).
    - hashimotonomora 5y ago
      False. Detectable is an experimental limitation of a given measurement system. Even one single virion can infect a host.
      - et2o 5y ago
        There is no data that supports this assertion whatsoever. There is a lot of evidence going against it. Theoretically it may be possible, but the probability of this is on the order of 0 and so close to 0 it will likely never happen. Think of it like chemistry. Sure, two covalently bonded hydrogen atoms at STP could have nuclei 1cm from each other due to random chance. However, the probability of this happening is so low that it is effectively 0.
        hashimotonomora 5y ago
        The assertion is still false then.
        mlyle 5y ago
        It's effectively true. If one bounds the risk from HIV from an undetectable partner to an unmeasurably small epsilon, dwarfed by other risks by many orders of magnitude--- the edges where the assertion are false don't matter.
    - mensetmanusman 5y ago
      It depends on if your body is able to detect it better than a machine…
  - chucksmash 5y ago
    Presumably the viral load required for transmission is greater than the viral load required for detection.
    - whimsicalism 5y ago
      My guess is it is more of a probabilistic thing than a strict threshold.
      - staticassertion 5y ago
        Yes. Super equals was inappropriate imo.
        whimsicalism 5y ago
        I don't know that it's inappropriate. I mean, technically, there's always a possibility of getting HIV. Particles in your body could spontaneously quantum tunnel at the same time into the form of an HIV virus. This is basically impossible, but not actually (p = 0.00) impossible. At some point you have to look at a probability and say - that's basically not transmissible.
    - stjohnswarts 5y ago
      That seems like a big if? maybe 0.5% of people actually are succeptable to the lowered viral load. Have studies been done that would detect such a population?
      - mlyle 5y ago
        One reason we believe this is that we can typically detect virus quantities way too small to reliably replicate in culture, and believe that in vivo infection is even harder than in culture (because of innate immune response and the body not being composed just of the most susceptible cells). You generally can't measure infectious dose directly without a highly unethical challenge study. You can sometimes know concentrations that did or didn't result in infection in various real world scenarios, and sometimes you have circumstantial evidence (e.g. you can know how much virus a person sheds, and what proportion of a room with certain ventilation quantities got infected).
  - Nbox9 5y ago
    CDC backing up this claim. Having an undetectable viral load prevents transmission during sex —- but likely not during needle sharing. The answer to why seems to be an obvious “because there are less virus particles”. I’m linking a couple of scientific studies following couples having condomless sex where one partner is HIV positive, on ART with low viral load. Among the about 2000 couples in these studies there were no transmissions. https://www.cdc.gov/hiv/basics/livingwithhiv/protecting-others.html https://www.cdc.gov/hiv/basics/livingwithhiv/protecting-othe... https://www.nejm.org/doi/full/10.1056/NEJMoa1600693#t=article https://www.nejm.org/doi/full/10.1056/NEJMoa1600693#t=articl... https://pubmed.ncbi.nlm.nih.gov/27404185/ https://pubmed.ncbi.nlm.nih.gov/27404185/
    - jl6 5y ago
      It does sound suspiciously like wishful thinking though, doesn’t it? You can’t sample all parts and all fluids of someone’s body all the time. Maybe trace undetectable levels of the virus can be transmitted, and of course they are going to look like a “no transmission” case if you lack the ability to detect that amount of virus. And that’s either not a problem (if trace levels = no symptoms), or a ticking time bomb waiting to find a host with the conditions that would enable mass viral replication back up to detectable levels.
      - throwaway22032 5y ago
        We feel fairly comfortable in stating that HIV is not transmissible surface-to-surface despite the mathematical fact that strictly there is some miniscule non-zero chance that it could be, this is basically the same thing.
      - lixtra 5y ago
        > You can’t sample all parts and all fluids of someone’s body all the time. Maybe trace undetectable levels of the virus can be transmitted… You don’t need to be a 100% sure. Once the risk becomes small enough you can spend your time worrying about other risks.
        jl6 5y ago
  - matheusmoreira 5y ago
    Viral load. Number of viral copies per volume of fluid. Merely exposing someone to a virus does not necessarily result in widespread infection. A low enough number of copies could be neutralized by the host's immune response before it has a chance to spread significantly. How low this number is depends on the virus. For example, COVID-19 load is higher in symptomatic patients. Chronic viral infections are managed by reducing as much as possible the number of viral copies in circulation. Risk of transmission is mitigated when number of copies is low enough. There are studies showing risk of HIV transmission approaches zero when HIV load < 200 copies/ml. Ideal would be HIV load < 50 copies/ml or undetectable. https://en.wikipedia.org/wiki/Viral_load https://en.wikipedia.org/wiki/Viral_load https://en.wikipedia.org/wiki/Minimal_infective_dose https://en.wikipedia.org/wiki/Minimal_infective_dose https://en.wikipedia.org/wiki/Management_of_HIV/AIDS https://en.wikipedia.org/wiki/Management_of_HIV/AIDS https://en.wikipedia.org/wiki/Viral_load_monitoring_for_HIV https://en.wikipedia.org/wiki/Viral_load_monitoring_for_HIV
    - hashimotonomora 5y ago
      At that low virion count it’s more about the probability that a virion will attach to the correct CD4 receptor and be able to work inside the cell. It’s not about the host's immune system defeating or being defeated on a number basis.
      - est31 5y ago
        To add to this, how many virions are needed for a successful replication to start depends on the virus. https://www.virology.ws/2011/01/21/are-all-virus-particles-infectious/ https://www.virology.ws/2011/01/21/are-all-virus-particles-i...
    - sampo 5y ago
      There is an "independent action hypothesis" in virology. It states that each virus particle (virion) has an independent probability of starting the infection in the body. https://royalsocietypublishing.org/doi/10.1098/rspb.2009.0064 https://royalsocietypublishing.org/doi/10.1098/rspb.2009.006...
  - astura 5y ago
    https://www.hiv.gov/blog/science-validates-undetectable-untransmittable-hiv-prevention-message https://www.hiv.gov/blog/science-validates-undetectable-untr...
  - inasio 5y ago
    Undetectable sometimes means less than 200 or less than 50 viral copies per ml (depending on device sensitivity). In contrast the peak in the acute phase is 10^7 copies per ml (and settles to around 10^5 in the chronic phase), the probability of transmission is infinitesimal. There are many studies following very high risk cohorts (sex workers, intravenous drug users, etc) that have been able to empirically confirm this.
- raducu 5y ago
  > And undetectable === untransmittable. Just in case people here didn't know. In no way saying this is not a good thing, but do we know if this can be sustained for the whole lifetime? Or is it that 20, 30 years later, as people get older the person eventually gets AIDS?
  - est31 5y ago
    As long as they take their daily ART pills, they are safe from AIDS in specific, which is basically a death sentence. But things are not black and white. Someone who has ever been HIV positive counts as immuno compromised for their entire life. Studies have shown that there is basically no shortening of life expectancy, if you start ART early enough in the process. > if the person with HIV started ART with a CD4 count above 500, they would be expected to live to the age of 87 – a little longer than those without HIV. https://www.aidsmap.com/news/mar-2020/yes-same-life-expectancy-hiv-negative-people-far-fewer-years-good-health https://www.aidsmap.com/news/mar-2020/yes-same-life-expectan...
    - sterlind 5y ago
      I've heard HIV patients describe ART as "aging" their organs. obviously preferable to dying horribly from AIDS, but still gnarly to contend with. it's really interesting to me that their health becomes poorer earlier, but that it doesn't affect mortality.
      - touisteur 5y ago
        This might maybe be because a lot of effort is now poured on mid to end of life care, with the improving life expectancy? So the science behind pushing along a decaying body gets better?
        sterlind 5y ago
        I sure hope so! I don't have HIV but I do have a genetic disorder that's wrecking my body. I'm determined to live as long as possible.
mariodiana 5y ago
I'm going from memory, and I can't remember how many years ago I saw this on television, but I thought it had something to do with a genetic mutation that likely gained a foothold in the Western European population sometime around the plague of the Middle Ages. If I remember correctly, if a person carried one copy of the gene, they could get infected with HIV, but it wouldn't develop into AIDS. If a person carried two copies, they would not even get infected with HIV. Anybody remember hearing something like this?

dillondoyle 5y ago

And undetectable === untransmittable. Just in case people here didn't know.

hdjjhhvvhga 5y ago
I didn't know this. Could you explain the reason?
- baq 5y ago
  No detectable virus means no transmissible virus.
  - Drdrdrq 5y ago
    To reiterate the question, why is that?
    - XzAeRosho 5y ago
      That's the million dollar question
    - JulianMorrison 5y ago
      Detection means there is enough virus physically present in the sample for the detection technology to identify it. Infection requires virus particles to be physically present in transmission vectors (fluids, droplets, etc). There's generally also a dose-response effect where more particles means more chance of evading the immune system well enough to establish replication in the victim. So a lack of anything to detect, means a lack of anything to spread an infection.
      - Drdrdrq 5y ago
        Thank you, makes sense!
      - _Microft 5y ago
        > So a lack of anything to detect, means a lack of anything to spread an infection. One should add that for that the threshold for detection has to be lower than the threshold for infection. Example: let the detection threshold be 10 particles/ml and the infection threshold be 100 particles/ml (*) -> then undetectable implies that it is very improbable that an infection will take place. (*) This is a very crude description. Think of it like this: Every single virion (virus particle) has a very low probability of causing an infection itself but there is a high number of them and for one them it might just work out (higher viral load -> higher risk of successful infection)
        hdjjhhvvhga 5y ago
        > One should add that for that the threshold for detection has to be lower than the threshold for infection. This statement is logical and makes perfect sense - but it's narrower than the original one.
    - space_fountain 5y ago
      I'm not a biologist and this is based on general knowledge and some quick google searches but: We're quite good at detecting viruses if we really want to. PCR can amplify DNA so much that we can detect even 50 viruses per milliliter of blood. A milliliter seems like actually a lot of blood to get into someone else and your innate immune system is capable of finding and neutralizing small amounts of contagions relatively well even if it's never seen it before. I do suspect this is a statistical impossibility though probably you could somehow get incredibly unlucky, for example in your blood momentarily all the free floating viruses end up in the same bit of blood and that somehow gets into someone else, but I think we can all realize that probability is tiny and in practice I don't think there are any examples of transmission with undetectable levels of HIV.
      - et2o 5y ago
        Well put. We can actually detect well below 50 copies/mL in the laboratory setting as well; we don’t go below this to maintain adequate test specificity and sensitivity in the clinical setting.
        space_fountain 5y ago
        Not to put you on the spot but from my cellular bio lab I took it felt like PCR should be capable of detecting literally a single example of the targeted bit of DNA in the sample. Is the problem with detecting below 50 that the sample is too easily contaminated or is it that the primers can spontaneously bind to things they aren't supposed to at a high enough rate to invalidate the results?
      - jagger27 5y ago
        > A milliliter seems like actually a lot of blood to get into someone else 1 cm^3 is indeed pretty big. That’s 1,000 little millimetre cubes, and we can detect as few as 50 virions in that space! I will point out though that 1 ml is low for semen (more like 2.5 ml or more).
  - hashimotonomora 5y ago
    False. Detectable is an experimental limitation of a given measurement system. Even one single virion can infect a host.
    - et2o 5y ago
      There is no data that supports this assertion whatsoever. There is a lot of evidence going against it. Theoretically it may be possible, but the probability of this is on the order of 0 and so close to 0 it will likely never happen. Think of it like chemistry. Sure, two covalently bonded hydrogen atoms at STP could have nuclei 1cm from each other due to random chance. However, the probability of this happening is so low that it is effectively 0.
      - hashimotonomora 5y ago
        The assertion is still false then.
        mlyle 5y ago
        It's effectively true. If one bounds the risk from HIV from an undetectable partner to an unmeasurably small epsilon, dwarfed by other risks by many orders of magnitude--- the edges where the assertion are false don't matter.
  - mensetmanusman 5y ago
    It depends on if your body is able to detect it better than a machine…
- chucksmash 5y ago
  Presumably the viral load required for transmission is greater than the viral load required for detection.
  - whimsicalism 5y ago
    My guess is it is more of a probabilistic thing than a strict threshold.
    - staticassertion 5y ago
      Yes. Super equals was inappropriate imo.
      - whimsicalism 5y ago
        I don't know that it's inappropriate. I mean, technically, there's always a possibility of getting HIV. Particles in your body could spontaneously quantum tunnel at the same time into the form of an HIV virus. This is basically impossible, but not actually (p = 0.00) impossible. At some point you have to look at a probability and say - that's basically not transmissible.
  - stjohnswarts 5y ago
    That seems like a big if? maybe 0.5% of people actually are succeptable to the lowered viral load. Have studies been done that would detect such a population?
    - mlyle 5y ago
      One reason we believe this is that we can typically detect virus quantities way too small to reliably replicate in culture, and believe that in vivo infection is even harder than in culture (because of innate immune response and the body not being composed just of the most susceptible cells). You generally can't measure infectious dose directly without a highly unethical challenge study. You can sometimes know concentrations that did or didn't result in infection in various real world scenarios, and sometimes you have circumstantial evidence (e.g. you can know how much virus a person sheds, and what proportion of a room with certain ventilation quantities got infected).
- Nbox9 5y ago
  CDC backing up this claim. Having an undetectable viral load prevents transmission during sex —- but likely not during needle sharing. The answer to why seems to be an obvious “because there are less virus particles”. I’m linking a couple of scientific studies following couples having condomless sex where one partner is HIV positive, on ART with low viral load. Among the about 2000 couples in these studies there were no transmissions. https://www.cdc.gov/hiv/basics/livingwithhiv/protecting-others.html https://www.cdc.gov/hiv/basics/livingwithhiv/protecting-othe... https://www.nejm.org/doi/full/10.1056/NEJMoa1600693#t=article https://www.nejm.org/doi/full/10.1056/NEJMoa1600693#t=articl... https://pubmed.ncbi.nlm.nih.gov/27404185/ https://pubmed.ncbi.nlm.nih.gov/27404185/
  - jl6 5y ago
    It does sound suspiciously like wishful thinking though, doesn’t it? You can’t sample all parts and all fluids of someone’s body all the time. Maybe trace undetectable levels of the virus can be transmitted, and of course they are going to look like a “no transmission” case if you lack the ability to detect that amount of virus. And that’s either not a problem (if trace levels = no symptoms), or a ticking time bomb waiting to find a host with the conditions that would enable mass viral replication back up to detectable levels.
    - throwaway22032 5y ago
      We feel fairly comfortable in stating that HIV is not transmissible surface-to-surface despite the mathematical fact that strictly there is some miniscule non-zero chance that it could be, this is basically the same thing.
    - lixtra 5y ago
      > You can’t sample all parts and all fluids of someone’s body all the time. Maybe trace undetectable levels of the virus can be transmitted… You don’t need to be a 100% sure. Once the risk becomes small enough you can spend your time worrying about other risks.
      - jl6 5y ago
- matheusmoreira 5y ago
  Viral load. Number of viral copies per volume of fluid. Merely exposing someone to a virus does not necessarily result in widespread infection. A low enough number of copies could be neutralized by the host's immune response before it has a chance to spread significantly. How low this number is depends on the virus. For example, COVID-19 load is higher in symptomatic patients. Chronic viral infections are managed by reducing as much as possible the number of viral copies in circulation. Risk of transmission is mitigated when number of copies is low enough. There are studies showing risk of HIV transmission approaches zero when HIV load < 200 copies/ml. Ideal would be HIV load < 50 copies/ml or undetectable. https://en.wikipedia.org/wiki/Viral_load https://en.wikipedia.org/wiki/Viral_load https://en.wikipedia.org/wiki/Minimal_infective_dose https://en.wikipedia.org/wiki/Minimal_infective_dose https://en.wikipedia.org/wiki/Management_of_HIV/AIDS https://en.wikipedia.org/wiki/Management_of_HIV/AIDS https://en.wikipedia.org/wiki/Viral_load_monitoring_for_HIV https://en.wikipedia.org/wiki/Viral_load_monitoring_for_HIV
  - hashimotonomora 5y ago
    At that low virion count it’s more about the probability that a virion will attach to the correct CD4 receptor and be able to work inside the cell. It’s not about the host's immune system defeating or being defeated on a number basis.
    - est31 5y ago
      To add to this, how many virions are needed for a successful replication to start depends on the virus. https://www.virology.ws/2011/01/21/are-all-virus-particles-infectious/ https://www.virology.ws/2011/01/21/are-all-virus-particles-i...
  - sampo 5y ago
    There is an "independent action hypothesis" in virology. It states that each virus particle (virion) has an independent probability of starting the infection in the body. https://royalsocietypublishing.org/doi/10.1098/rspb.2009.0064 https://royalsocietypublishing.org/doi/10.1098/rspb.2009.006...
- astura 5y ago
  https://www.hiv.gov/blog/science-validates-undetectable-untransmittable-hiv-prevention-message https://www.hiv.gov/blog/science-validates-undetectable-untr...
- inasio 5y ago
  Undetectable sometimes means less than 200 or less than 50 viral copies per ml (depending on device sensitivity). In contrast the peak in the acute phase is 10^7 copies per ml (and settles to around 10^5 in the chronic phase), the probability of transmission is infinitesimal. There are many studies following very high risk cohorts (sex workers, intravenous drug users, etc) that have been able to empirically confirm this.
raducu 5y ago
> And undetectable === untransmittable. Just in case people here didn't know. In no way saying this is not a good thing, but do we know if this can be sustained for the whole lifetime? Or is it that 20, 30 years later, as people get older the person eventually gets AIDS?
- est31 5y ago
  As long as they take their daily ART pills, they are safe from AIDS in specific, which is basically a death sentence. But things are not black and white. Someone who has ever been HIV positive counts as immuno compromised for their entire life. Studies have shown that there is basically no shortening of life expectancy, if you start ART early enough in the process. > if the person with HIV started ART with a CD4 count above 500, they would be expected to live to the age of 87 – a little longer than those without HIV. https://www.aidsmap.com/news/mar-2020/yes-same-life-expectancy-hiv-negative-people-far-fewer-years-good-health https://www.aidsmap.com/news/mar-2020/yes-same-life-expectan...
  - sterlind 5y ago
    I've heard HIV patients describe ART as "aging" their organs. obviously preferable to dying horribly from AIDS, but still gnarly to contend with. it's really interesting to me that their health becomes poorer earlier, but that it doesn't affect mortality.
    - touisteur 5y ago
      This might maybe be because a lot of effort is now poured on mid to end of life care, with the improving life expectancy? So the science behind pushing along a decaying body gets better?
      - sterlind 5y ago
        I sure hope so! I don't have HIV but I do have a genetic disorder that's wrecking my body. I'm determined to live as long as possible.

mariodiana 5y ago

I'm going from memory, and I can't remember how many years ago I saw this on television, but I thought it had something to do with a genetic mutation that likely gained a foothold in the Western European population sometime around the plague of the Middle Ages. If I remember correctly, if a person carried one copy of the gene, they could get infected with HIV, but it wouldn't develop into AIDS. If a person carried two copies, they would not even get infected with HIV. Anybody remember hearing something like this?