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Posted On: 10/16/2024 5:43:14 AM
Post# of 148018
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Possibly but a decrease in log of 1.77 compared to what?
In comparison to the viral load at the time of drug injection.
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I’m assuming what I’m reading tells me that PGT 121 Is a gp120 Blocker? If that’s the case, you are blocking both receptors that HIV binds to to enter a T cell. I.e., you are blocking CCR5 and gp120. I don’t think you need both unless you were involving CXCR4 (maybe not) and maybe Ohm can contribute here.
If one of those two receptors is inhibited, then the other one does not work to allow HIV into the cell. I believe this is a co-receptor scenario.
Your post stated that PGT 121 Is located distally from the gp 120 epitope So maybe that makes it not crucial to the co-receptor with gp120 and CCR5 connection.
Regardless, if PGT 121 Is an entry inhibitor owned by ViiV It makes me very curious why they are using it with LL other than my curiosity that it is distally located from the GP 120 receptor.
Ohm, Why I have two entry inhibitors on board?
PGT121-LS and VRC07-523-LS both bind to the gp120 site on the HIV virus and block it from attaching to the CD4 receptor on CD4 immune cells. Two bNAbs are used because the virus can develop resistance to bNAbs and is less likely to do so when used in combination. bNAbs combined with ART do maintain very good viral control but once you remove ART the virus rebounds significantly. Which shows that bNAbs imperfectly control attachment to the CD4 receptor.
Why I think the leronlimab, ART does a very quick knockdown of the virus. bNAbs because of the gp120 attachment are probably a little quicker acting than leronlimab in blocking but it's an imperfect blocking. Leronlimab covers any blocking that bNAbs miss meaning that there's not an explosion of the virus and very few chances for HIV reservoirs to develop. It has been shown that maraviroc and thus leronlimab can flush the virus out of reservoirs to some extent. What few reservoirs that do exist and release the virus would soon see the virus killed by ART or blocked by the bNAbs or leronlimab.
Short-term combination immunotherapy with broadly neutralizing antibodies
and CCR5 blockade mediates ART-free viral control in infant rhesus macaques
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