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Assuming you could, wouldn't the immune system lose that fight? It specifically attacks the immune system after all. deliberately increasing HIV viral load woul

Assuming you could, wouldn't the immune system lose that fight? It specifically attacks the immune system after all. deliberately increasing HIV viral load would probably be on the same level of danger as nuking someone's bone-marrow to prepare for a bone-marrow transplant. HIV is also a retrovirus which means it embeds its genetic code into host cell DNA. It can't be cured simply by getting rid of all present viruses.

jljljl 4y ago
Assuming it could be done, I think you'd activate the reservoir, then bombard the patient with anti-retrovirals until the virus was eradicated?
- John23832 4y ago
  This is correct. You'd just get infected cells in the reservoir to express so that they can be identified and killed. That's what an outbreak is, viral expression. This is similar to how HSV outbreaks work. Your entire body isn't massively infected, the virus is just expressing. People often confuse an "outbreak" with "massive infection".
- m0llusk 4y ago
  That is an approach being tried for a cure. So far it has not worked. It is not clear exactly why.
- jjtheblunt 4y ago
  How would that excise the viral sequence from the already rewritten dna in cells previously infected, rather than just slow further new uninflected cells from being infected? The point is, in the presence of a retrovirus with its reverse transcriptase trickery, an organism is a chimera, populated by dna-distinct cells (for example, never infected cells vs cells previously infected and thereby holding modified dna, who would send out new virus during their own replication).
  - jljljl 4y ago
    The "assuming it could be done" in my comment referred to "finding a way to force latent cells to release their viral load rather than remaining latent". I'm not an immunologist, but if there was a mechanism, it would probably kill the rewritten cells. Then the released viruses would be eliminated with anti-retrovirals. If this same mechanism kept infected cells from remaining latent, eventually you would clear the virus. So I don't know the answer to your question, but my answer was assuming an answer existed :)
  - f6v 4y ago
    Several things come to mind. First, you don’t need to remove viral DNA from cells. Just make them over-express HIV and trigger cytotoxic lymphocytes or antibody-mediated killing. You end up wiping all the infected cells. But then, of course, patient is left with compromised immunity. To solve this, you could make a stem cell transplant from a compatible donor. Alternatively, harvest healthy cells before the treatment and transplant them back after. This is from the top of my had, I’m not an expert in the field.
    - John23832 4y ago
      Your body would eventually replace the Helper T-Cells lost, but yes, we'd probably want to do some mitigation for safety.
      - f6v 4y ago
        > Your body would eventually replace the Helper T-Cells lost With thymus involution?
John23832 4y ago
> Assuming you could, wouldn't the immune system lose that fight? It specifically attacks the immune system after all. deliberately increasing HIV viral load would probably be on the same level of danger as nuking someone's bone-marrow to prepare for a bone-marrow transplant. HIV kills in the long term. The human body fights very well against HIV, it just exhausts its resources. One massive "outbreak" (I have no idea what that would look like), would be essentially laying out all of the HIV to the immune system saying "Here. Now do something about all of this." > HIV is also a retrovirus which means it embeds its genetic code into host cell DNA. It can't be cured simply by getting rid of all present viruses. T-Cells remove infected cells. That would be the mechanism of removal from the body.
- bregma 4y ago
  Since HIV infects T-cells, ramping up the T-cells to kill the T-cells will result in a higher viral load leading to an out-of-control spiral, and certain death. That's how HIV kills in the first place.
  - John23832 4y ago
    I’m not an expert on HIV, but that's not correct. HIV infects your helper T cells. Helper T cells activate your B cells which create antibodies that alert for intrusions. Those antibodies then cause your Killer T cells to act (actually kill and remove intruders). HIV basically causes your Helper T-Cells to die (quicker than they are naturally replaced by the body) causing an under-reaction (and eventually no reaction) by your B cells (which then means there are no antibodies for your Killers to act on). Essentially your immune system is turned off. This allows for opportunistic infections which are what actually kills you. That’s the resource exhaustion that I was referencing. This is also why there is a focus on keeping CD4+ (Helper) T-cell levels high. You want your immune system to keep responding to outside threats. An HIV outbreak would not mean that all of your Helper T-Cells are infected. It means that HIV in the viral reservoirs are active. Actively producing Helper T-Cells are cells that your body could then target. Killers would kill the affected Helpers, but your body would reproduce Helpers. The goal would be to allow your body to "be able to see" all of the infected Helpers.
deleted 4y ago
[deleted]

jljljl 4y ago

Assuming it could be done, I think you'd activate the reservoir, then bombard the patient with anti-retrovirals until the virus was eradicated?

John23832 4y ago
This is correct. You'd just get infected cells in the reservoir to express so that they can be identified and killed. That's what an outbreak is, viral expression. This is similar to how HSV outbreaks work. Your entire body isn't massively infected, the virus is just expressing. People often confuse an "outbreak" with "massive infection".
m0llusk 4y ago
That is an approach being tried for a cure. So far it has not worked. It is not clear exactly why.
jjtheblunt 4y ago
How would that excise the viral sequence from the already rewritten dna in cells previously infected, rather than just slow further new uninflected cells from being infected? The point is, in the presence of a retrovirus with its reverse transcriptase trickery, an organism is a chimera, populated by dna-distinct cells (for example, never infected cells vs cells previously infected and thereby holding modified dna, who would send out new virus during their own replication).
- jljljl 4y ago
  The "assuming it could be done" in my comment referred to "finding a way to force latent cells to release their viral load rather than remaining latent". I'm not an immunologist, but if there was a mechanism, it would probably kill the rewritten cells. Then the released viruses would be eliminated with anti-retrovirals. If this same mechanism kept infected cells from remaining latent, eventually you would clear the virus. So I don't know the answer to your question, but my answer was assuming an answer existed :)
- f6v 4y ago
  Several things come to mind. First, you don’t need to remove viral DNA from cells. Just make them over-express HIV and trigger cytotoxic lymphocytes or antibody-mediated killing. You end up wiping all the infected cells. But then, of course, patient is left with compromised immunity. To solve this, you could make a stem cell transplant from a compatible donor. Alternatively, harvest healthy cells before the treatment and transplant them back after. This is from the top of my had, I’m not an expert in the field.
  - John23832 4y ago
    Your body would eventually replace the Helper T-Cells lost, but yes, we'd probably want to do some mitigation for safety.
    - f6v 4y ago
      > Your body would eventually replace the Helper T-Cells lost With thymus involution?

John23832 4y ago

> Assuming you could, wouldn't the immune system lose that fight? It specifically attacks the immune system after all. deliberately increasing HIV viral load would probably be on the same level of danger as nuking someone's bone-marrow to prepare for a bone-marrow transplant. HIV kills in the long term. The human body fights very well against HIV, it just exhausts its resources. One massive "outbreak" (I have no idea what that would look like), would be essentially laying out all of the HIV to the immune system saying "Here. Now do something about all of this." > HIV is also a retrovirus which means it embeds its genetic code into host cell DNA. It can't be cured simply by getting rid of all present viruses. T-Cells remove infected cells. That would be the mechanism of removal from the body.

bregma 4y ago
Since HIV infects T-cells, ramping up the T-cells to kill the T-cells will result in a higher viral load leading to an out-of-control spiral, and certain death. That's how HIV kills in the first place.
- John23832 4y ago
  I’m not an expert on HIV, but that's not correct. HIV infects your helper T cells. Helper T cells activate your B cells which create antibodies that alert for intrusions. Those antibodies then cause your Killer T cells to act (actually kill and remove intruders). HIV basically causes your Helper T-Cells to die (quicker than they are naturally replaced by the body) causing an under-reaction (and eventually no reaction) by your B cells (which then means there are no antibodies for your Killers to act on). Essentially your immune system is turned off. This allows for opportunistic infections which are what actually kills you. That’s the resource exhaustion that I was referencing. This is also why there is a focus on keeping CD4+ (Helper) T-cell levels high. You want your immune system to keep responding to outside threats. An HIV outbreak would not mean that all of your Helper T-Cells are infected. It means that HIV in the viral reservoirs are active. Actively producing Helper T-Cells are cells that your body could then target. Killers would kill the affected Helpers, but your body would reproduce Helpers. The goal would be to allow your body to "be able to see" all of the infected Helpers.

deleted 4y ago

[deleted]