Quote:In HIV, the chronic inflammation which arises is not a result of an overactive immune state.
Chronic inflammation is always caused by an overactive immune system. In HIV patients on ART there are three main causes. Damage to intestinal walls during the active phase of HIV. Persistent HIV virus due to HIV virus reservoirs. As you mention other diseases can arise during the HIV active phase and even those that existed prior.
A wide array of inflammatory factors that leronlimab can control are elevated in PLWH individuals. There is also an imbalanced CD4/CD8 cell count in those with chronic inflammation which is usually typified by a low CD4 count along with a high CD8 count. As shown by Dr. Sacha the use of leronlimab can increase CD4 cell counts in patients with HIV. Patterson's work show's leronlimab can address the CD4/CD8 imbalance. CCR5 also helps differentiate CD8 T-cells into types. We know leronlimab pushes a TH1 cell differentiation which is pro-inflammatory but then knocks down the specific inflammatory factors. That may explain the immunomodulatory rather than immunosuppressive effect. It's probably something I should dig into but I don't know whether I want to go down another rabbit hole for a year.
Quote:"So a vaccine, a cold, a herpes outbreak, clinical or subclinical, any sort of illness can turn the virus back on." He says, "blipping occurs with any immune activation event" and that is very bad because the person becomes infectious again."
Those blips while using leronlimab may have two causes. The other infection may cause a rapid rise in CCR5 that leronlimab does not cover in time and/or it causes HIV viral reservoirs to release their stores of HIV virus. If it's the first, leronlimab will eventually occupy all CCR5 again and stop further reproduction. If it's the second, then that released virus will have no CCR5 open with which to reproduce. Either way it would explain why the virus goes back down with continued use of leronlimab.
Quote:"Inflammation shows that immune system components are not present and in place or are being depleted because they are actively dealing with some infectious agents. AIDS doesn't kill you - a deficient immune system kills you. AIDS means you will have Chronic Immune Activation Inflammation that will result in clots, strokes, heart attacks, liver and kidney failure, gut diseases, etc.
CD4+ and CD8+ cells are especially important to restore to homeostasis. HIV directly destroys CD4+ cells through the CCR5 receptor and CD8+ cells are depleted to exhaustion by RANTES. They work together in a certain ratio/balance. Restoring that balance is one of the most important things that LL does. I don't think inflammation can be stopped without that balance."
This references an active HIV infection. Under ART treatment you can see a low CD4 count along with a high CD8 count. Some will have a very good CD4 count along with a high CD8 count which will show more of a balance but it's still in an overreactive immune state. You want to see a normal state for both in relation to any current infections.
Quote:Inflammation occurs as a result of the immune system components being either continuously depleted (as in the case of HIV/AIDS) or continuously consumed in fighting off other targets or unnecessary targets (AutoImmune Disease).
In active HIV expression and less so in chronic inflammation you will see older T cells with an overexpression of CD57. CD57 slows down the replication of T cells but not the creation of new ones thus the exhaustion. Interestingly PD-1 expression and TGF-b are associated with T-cell exhaustion and leronlimab downregulates both.
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