Thanks ohm.
I'll take this a bit further.
Reference is made to the following:
https://www.frontiersin.org/articles/10.3389/...;id=794638
In discussing the Receptor Occupancy of LL in HIV, (I know HIV is not a chemokine, however, it still has strong binding affinity to CCR5), this statement seems to say that LL prevents all HIV from binding to CCR5.
Fully suppressed = No HIV in the plasma means no HIV in the CD4 cells which means No HIV bound to CCR5.
Full LL RO on CCR5 of CD4 T cells.
Complete LL RO = no HIV binding to CCR5
The statistically significant increase in CCR5+CD4+T cells in peripheral blood is akin/reminiscent of the findings in the UCLA Long Covid Study where LL dosing increased quantities of CCR5 receptors on the surfaces of the immune cells.
They pointed out:
And for the time duration:
This almost gives the indication that if you administer LL for longer periods, its half-life also increases:
back to original point:
I'll take this a bit further.
Reference is made to the following:
https://www.frontiersin.org/articles/10.3389/...;id=794638
In discussing the Receptor Occupancy of LL in HIV, (I know HIV is not a chemokine, however, it still has strong binding affinity to CCR5), this statement seems to say that LL prevents all HIV from binding to CCR5.
Quote:Weekly Leronlimab treatment in a chronically SIV-infected macaque led to increased CCR5+CD4+ T cells levels and fully suppressed plasma viremia, both concomitant with full CCR5 RO on peripheral blood CD4+ T cells, demonstrating that CCR5+CD4+ T cells were protected from viral replication by Leronlimab binding.
Fully suppressed = No HIV in the plasma means no HIV in the CD4 cells which means No HIV bound to CCR5.
Full LL RO on CCR5 of CD4 T cells.
Quote:Finally, we extended these results to Leronlimab-treated humans and found that weekly 700 mg Leronlimab led to complete CCR5 RO on peripheral blood CD4+ T cells and a statistically significant increase in CCR5+CD4+ T cells in peripheral blood.
Complete LL RO = no HIV binding to CCR5
The statistically significant increase in CCR5+CD4+T cells in peripheral blood is akin/reminiscent of the findings in the UCLA Long Covid Study where LL dosing increased quantities of CCR5 receptors on the surfaces of the immune cells.
They pointed out:
Quote:Following treatment with Leronlimab, we found increased frequencies of CCR5+CD4+ T cells where CCR5 was resistant to internalization following treatment with all three CCR5 ligands, indicating that Leronlimab both stabilized surface CCR5 expression and prevented its internalization. Thus, it is critical to account for this Leronlimab-induced increase in surface CCR5 levels for CCR5 RO measurements.
And for the time duration:
Quote:Leronlimab treatment yielded full CCR5 RO on peripheral blood CD4+ T cells by eight hours post injection, and maintained >90% CCR5 RO for an average of 12.8 days and 32.6 days for the 10 mg/kg and 50 mg/kg groups, respectively (Figure 3B).
This almost gives the indication that if you administer LL for longer periods, its half-life also increases:
Quote:Importantly, the increased frequencies of CCR5+CD4+ T cell targets did not exacerbate SIV replication. Instead, Leronlimab potently and completely suppressed SIV replication from 1st injection to approximately 20 weeks, (after giving it weekly for 11 weeks), during the time period where both full CCR5 RO and increased CCR5+CD4+ T cells were present in the blood (Figure 4D). As the Leronlimab plasma concentration declined and CCR5 RO was lost on CD4+ T cells, viral rebound occurred. SIVmac239 plasma viremia ultimately returned to pre-Leronlimab levels after complete loss of CCR5 RO. Therefore, the Leronlimab-induced increase in CCR5+CD4+ T cell targets did not exacerbate ongoing SIV replication; rather, the binding of Leronlimab to the CCR5 co-receptor used for viral entry protected these cells from infection and greatly diminished ongoing SIV replication, resulting in minimal plasma viremia during the period of complete CCR5 RO.
back to original point:
Quote:Both suppression of viral replication and increased CCR5+CD4+ T cell levels were temporally associated with full CCR5 RO on peripheral blood CD4+ T cells, underscoring the need to measure CCR5 RO in studies utilizing CCR5-blocking agents.
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