6 ms·

TLDR edited down from https://hivinfo.nih.gov/understanding-hiv/fact-sheets/what-latent-hiv-reservoir https://hivinfo.nih.gov/understanding-hiv/fact-sheets/what

TLDR edited down from https://hivinfo.nih.gov/understanding-hiv/fact-sheets/what-latent-hiv-reservoir https://hivinfo.nih.gov/understanding-hiv/fact-sheets/what-l... (I couldn't read TFA because uMatrix) Finding ways to target and destroy latent reservoirs is a challenge facing HIV researchers Some HIV-infected immune cells go into a resting or latent state. While in this resting state, the infected cells do not produce new virus. A latent HIV reservoir is a group of immune system cells in the body that are infected with HIV but are not actively producing new HIV. HIV medicines prevent HIV from multiplying, which reduces the amount of the virus in the body (called the viral load). Because the HIV-infected cells in a latent reservoir are not producing new copies of the virus, HIV medicines have no effect on them. People with HIV must take a daily combination of HIV medicines (called an HIV treatment regimen) to keep their viral loads low. If a person stops taking their HIV medicines, the infected cells of the latent reservoir can begin making HIV again and the person's viral load will increase. That is why it is important to continue taking HIV medicines every day as prescribed, even when viral load levels are low. Finding ways to target and destroy latent reservoirs is a major challenge facing HIV researchers. Researchers are exploring different strategies for clearing out reservoirs, including: Using gene therapy (manipulating genes to treat or prevent disease) to cut out certain HIV genes and inactivate the virus in HIV-infected immune cells. Developing drugs or other methods to reactivate latent HIV so that the HIV can be destroyed by the immune system or new HIV therapies. This means of eliminating latent HIV reservoirs is sometimes known as the “shock and kill” or “kick and kill” strategy.

deleted 4y ago
[deleted]
bsder 4y ago
Hopefully this kind of research to go after "latent reservoirs" will bleed over into figuring out how to wipe out Herpes virii as well.
- amluto 4y ago
  If you believe these people, ADCC (antibody-dependent cellular cytotoxicity) is sufficient to both prevent and clear HSV, and an appropriate vaccine can induce the appropriate antibodies to pull it off. https://x-vax.com/ https://x-vax.com/ Of course, this seems to be suffering the usual fate of any vaccine technology other than spiffy mRNA vaccines against extremely urgent and well funded diseases: a neat proof of concept and some pre-clinical studies happen, followed by years of radio silence.
  - XorNot 4y ago
    It's not like HIV is the easiest virus to test a vaccine against. A clinical trial against COVID is pretty ethically sound: provided the vaccine is harmless, the novel virus which most people still survive is survivable. With HIV, if the vaccine is harmless, you're still left with the fact that failure means a bunch of people get an incurable, fatal disease. HIV vaccine trials are costly and lengthy: you take a statistically at-risk population, vaccinate half, and then tell them to not assume the vaccine works, but a decent number of them are likely to (1) assume it does and (2) engage or be victimized by risky activity which leads to some of them getting HIV. At the end of that, you then tally up your groups and see if you see a substantial difference in who is now HIV positive. I can't imagine how much it sucks to be involved in the planning of those experiments. Someone, somewhere, talks to every single one of the people involved knowing full well what might happen.
    - amluto 4y ago
      My post and the GP were about HSV (herpes simplex virus), not HIV. HSV is extremely prevalent, so a simple randomized controlled trial in children should do the trick. (And there isn’t even any substantial ethical issue with participants potentially taking addition risks — kids don’t do anything to avoid HSV in the first place.) But the specific discussion is about a potential cure. Finding a few hundred HSV patients who don’t take any antivirals when they don’t have any lesions should be very, very easy as trials go — something like half the population is seropositive, many of those have occasional symptoms, and very few of those are taking antivirals to prevent symptoms.
    - 4y ago
AnthonBerg 4y ago
Here’s the paper the article discusses: “Rebound virus in the cerebrospinal fluid reveals a possible HIV-1 reservoir” in Nature Microbiology – https://doi.org/10.1038/s41564-022-01309-3 https://doi.org/10.1038/s41564-022-01309-3 Which is a summary of the paper “Rebound HIV-1 in cerebrospinal fluid after antiviral therapy interruption is mainly clonally amplified R5 T cell-tropic virus” by Kincer, L.P., Joseph, S.B., Gilleece, M.M. et al. – https://doi.org/10.1038/s41564-022-01306-6 https://doi.org/10.1038/s41564-022-01306-6
kerpotgh 4y ago
[dead]
inasio 4y ago
Latent reservoirs are super interesting. They've seen in experiments that they keep copies of all of the HIV strains that infected people go through (HIV is one of the viruses with the highest mutation rates). When people have gone off meds sometimes they've managed to sample their blood and seen how all of this viral strains activate around the same time.
- __blockcipher__ 4y ago
  To be clear, I imagine that it’s not that the reservoir is literally “intentionally” storing different strains but just that viruses are more accurately thought of as “quasispecies swarms”: https://en.wikipedia.org/wiki/Viral_quasispecies https://en.wikipedia.org/wiki/Viral_quasispecies This is a naturally emergent phenomena. (Just adding some further context to what you were saying)
moremetadata 4y ago
I read this and I wonder why something like dialysis machines couldn't be adapted to filter the blood, recreating an artificial environment in which to attract infected CD4 cells. I read a study from around the time of WW1 because blood banks didnt exists then, which is when MDMA aka Ecstasy was invented (for blood clotting purposes) one experiment drained all the blood from a dog, and replaced it with isotonic saline solution. 24hrs later about half the solution had been replaced with blood cells. There was no comment on what effect it had on other parts of the body, like the brain considering the oxygen carrying capacity of the blood. They dont go into detail about which type of CD4+ T cells, there are different types of these cells. Sodium intake will increase Th17 cells which contributes to a class of diseases called autoimmune like arthritis. Its a bit too vague for my liking, and as cells differentiate into different types of cells, the virus must be present somewhere else yet to be detected. This virus sounds like bacteria going dormant in the body by forming biofilms until conditions are right in order to activate again, a risk with antibiotic use and no phage treatment. In fact I wonder if phages have been used to target other virally infected cells, shall have to look that up. 1ml of seawater contains billions of phages. Neutrophils are the only part of the innate immune system I know of which targets pathogens like bacterial biofilms, viruses & foreign objects. Omega 3 EPA & DHA increase in the neutrophil membrane content to make it more effective at targeting pathogens, the higher content also increases the size of the neutrophil making it possible to target larger pathogens. EPA (and possibly ETA a COX inhibitor) also down regulates the osteoclasts, helping to protect and seal the bones, which is where these bone marrow stem cell derived immune cells come from. Once your bones integrity starts to fail, other (adaptive) immune cells get in and start attacking the bone marrow causing the autoimmune diseases. I've seen studies using 8grams a day of Omega 3's ! Histidine/Carnosine would also compliment Omega-3 intake. Now its always been my understanding there are parts of the body CD4 T helper cells cant go, like brain, eyes (eg causing blindness within seconds), testes and ovaries, so to see it mentioned that CD4+ cells are found in the spinal fluid, makes me wonder if there is some sort of blood brain barrier integrity breakdown occurred or is this a Nucleic Acid Amplification Test error, like the type seen with the Covid PCR testing? The CSF is very slow to change as well, it takes weeks and months to get nutrients into CSF compared to other parts of the body. Still interesting none the less.
- 4y ago

deleted 4y ago

[deleted]

bsder 4y ago

Hopefully this kind of research to go after "latent reservoirs" will bleed over into figuring out how to wipe out Herpes virii as well.

amluto 4y ago
If you believe these people, ADCC (antibody-dependent cellular cytotoxicity) is sufficient to both prevent and clear HSV, and an appropriate vaccine can induce the appropriate antibodies to pull it off. https://x-vax.com/ https://x-vax.com/ Of course, this seems to be suffering the usual fate of any vaccine technology other than spiffy mRNA vaccines against extremely urgent and well funded diseases: a neat proof of concept and some pre-clinical studies happen, followed by years of radio silence.
- XorNot 4y ago
  It's not like HIV is the easiest virus to test a vaccine against. A clinical trial against COVID is pretty ethically sound: provided the vaccine is harmless, the novel virus which most people still survive is survivable. With HIV, if the vaccine is harmless, you're still left with the fact that failure means a bunch of people get an incurable, fatal disease. HIV vaccine trials are costly and lengthy: you take a statistically at-risk population, vaccinate half, and then tell them to not assume the vaccine works, but a decent number of them are likely to (1) assume it does and (2) engage or be victimized by risky activity which leads to some of them getting HIV. At the end of that, you then tally up your groups and see if you see a substantial difference in who is now HIV positive. I can't imagine how much it sucks to be involved in the planning of those experiments. Someone, somewhere, talks to every single one of the people involved knowing full well what might happen.
  - amluto 4y ago
    My post and the GP were about HSV (herpes simplex virus), not HIV. HSV is extremely prevalent, so a simple randomized controlled trial in children should do the trick. (And there isn’t even any substantial ethical issue with participants potentially taking addition risks — kids don’t do anything to avoid HSV in the first place.) But the specific discussion is about a potential cure. Finding a few hundred HSV patients who don’t take any antivirals when they don’t have any lesions should be very, very easy as trials go — something like half the population is seropositive, many of those have occasional symptoms, and very few of those are taking antivirals to prevent symptoms.
  - 4y ago

AnthonBerg 4y ago

Here’s the paper the article discusses: “Rebound virus in the cerebrospinal fluid reveals a possible HIV-1 reservoir” in Nature Microbiology – https://doi.org/10.1038/s41564-022-01309-3 https://doi.org/10.1038/s41564-022-01309-3 Which is a summary of the paper “Rebound HIV-1 in cerebrospinal fluid after antiviral therapy interruption is mainly clonally amplified R5 T cell-tropic virus” by Kincer, L.P., Joseph, S.B., Gilleece, M.M. et al. – https://doi.org/10.1038/s41564-022-01306-6 https://doi.org/10.1038/s41564-022-01306-6

kerpotgh 4y ago

[dead]

inasio 4y ago

Latent reservoirs are super interesting. They've seen in experiments that they keep copies of all of the HIV strains that infected people go through (HIV is one of the viruses with the highest mutation rates). When people have gone off meds sometimes they've managed to sample their blood and seen how all of this viral strains activate around the same time.

__blockcipher__ 4y ago
To be clear, I imagine that it’s not that the reservoir is literally “intentionally” storing different strains but just that viruses are more accurately thought of as “quasispecies swarms”: https://en.wikipedia.org/wiki/Viral_quasispecies https://en.wikipedia.org/wiki/Viral_quasispecies This is a naturally emergent phenomena. (Just adding some further context to what you were saying)

moremetadata 4y ago

I read this and I wonder why something like dialysis machines couldn't be adapted to filter the blood, recreating an artificial environment in which to attract infected CD4 cells. I read a study from around the time of WW1 because blood banks didnt exists then, which is when MDMA aka Ecstasy was invented (for blood clotting purposes) one experiment drained all the blood from a dog, and replaced it with isotonic saline solution. 24hrs later about half the solution had been replaced with blood cells. There was no comment on what effect it had on other parts of the body, like the brain considering the oxygen carrying capacity of the blood. They dont go into detail about which type of CD4+ T cells, there are different types of these cells. Sodium intake will increase Th17 cells which contributes to a class of diseases called autoimmune like arthritis. Its a bit too vague for my liking, and as cells differentiate into different types of cells, the virus must be present somewhere else yet to be detected. This virus sounds like bacteria going dormant in the body by forming biofilms until conditions are right in order to activate again, a risk with antibiotic use and no phage treatment. In fact I wonder if phages have been used to target other virally infected cells, shall have to look that up. 1ml of seawater contains billions of phages. Neutrophils are the only part of the innate immune system I know of which targets pathogens like bacterial biofilms, viruses & foreign objects. Omega 3 EPA & DHA increase in the neutrophil membrane content to make it more effective at targeting pathogens, the higher content also increases the size of the neutrophil making it possible to target larger pathogens. EPA (and possibly ETA a COX inhibitor) also down regulates the osteoclasts, helping to protect and seal the bones, which is where these bone marrow stem cell derived immune cells come from. Once your bones integrity starts to fail, other (adaptive) immune cells get in and start attacking the bone marrow causing the autoimmune diseases. I've seen studies using 8grams a day of Omega 3's ! Histidine/Carnosine would also compliment Omega-3 intake. Now its always been my understanding there are parts of the body CD4 T helper cells cant go, like brain, eyes (eg causing blindness within seconds), testes and ovaries, so to see it mentioned that CD4+ cells are found in the spinal fluid, makes me wonder if there is some sort of blood brain barrier integrity breakdown occurred or is this a Nucleic Acid Amplification Test error, like the type seen with the Covid PCR testing? The CSF is very slow to change as well, it takes weeks and months to get nutrients into CSF compared to other parts of the body. Still interesting none the less.

4y ago