Quote:does our Vyrologix prevent the ongoing establishment of LATENT HIV-1 reservoirs of the monoclonals directed at CCR5 that have been investigated.
With 100% receptor occupancy it would lower the establishment of new latent cells dramatically. Direct cell to cell HIV transmission has been brought up. But this is obviously a minor form of transmission, if it wasn't leronlimab wouldn't be able to control HIV.
BET inhibitors have the ability to flush out latent HIV if done sufficiently enough blocking by leronlimab could stop all but cell to cell transmission. With ever decreasing HIV expression and diminishing cell to cell transmission leronlimab could eliminate HIV reproduction over time.
Working against that is leronlimab itself. mTOR promotes latent HIV activation, leronlimab downregulates mTOR and would repress latent cells from activating, which could explain part of leronlimab's high efficacy. So whether forced activation by BET inhibitors is viable depends on whether it would overcome the effects of mTOR downregulation.
It does bring light to the very first thing I mentioned about leronlimab potentially being a cure back in May 2019. Anything under 40 copies per ml is what the FDA considers effective in HIV. In monotherapy we had some patients that were .4 copies per ml. I still don't know whether that .4 copies was from very long term patients.
Quote:CD4+ memory T-cells (where hidden HIV reservoirs hide) differentiate themselves after the naive CD4+ T-cells are already produced and in response to an event. As long as there are any CD4+ cells with active CCR5 receptors than CCR5 specific HIV can reproduce when the hidden reservoirs of HIV activate.
With CD32 T-cells there are no CCR5 receptors. With bone marrow transplants chemo will destroy the existing blood producing cells so any replacement with CD32 variant will only produce non-CCR5 expressive T-cells. There will be no place for HIV to latch on and replicate.
Since the reservoirs exist outside of the marrow a non-CD32 transplant will not stop HIV.
Best case scenario - The half life of CD4+ memory T-cells is 44 months. Without a virological event leronlimab may be able to block all CCR5 receptors, keeping new CD4+ memory T-cells from becoming infected. So every 44 months, under best conditions, half the reservoir ceases to exist. Over a very long period of time leronlimab may effectuate a cure.
https://investorshangout.com/post/view?id=5440017
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