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Posted On: 11/23/2020 8:08:18 PM
Post# of 148902
Gotta wonder if a cure is possible. Certainly the Berlin and London patients are encouraging that it can be replicated. Apparently need to get the virus eliminated from the CD4+ T memory cells:
https://www.cell.com/immunity/fulltext/S1074-7613(18)30201-2
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154081/
Myelosuppression prior to bone marrow transplant helps bring the CD4+ T-memory cell reservoir down, but I wonder if it will be enough?
I think any "cure" will need to involve a "kick and kill" type strategy to reactivate the latent virus while protecting new cells (with CCR5 antagonists or CCR5 gene editing / knockout), allowing the immune system to wipe out the viral reservoir while keeping the re-activated virus from spreading.
Have been an investor in SGMO for a while with their efforts at CCR5 KO, and ongoing trials to look at the effects on higher editing (blocking more cells from HIV infection by editing CCR5 out of a higher percentage of immune cells), it has been challenging to keep HIV viral load down with CCR5 knockout. Maybe they just haven't done it well enough, and leronlimab plus myeloablative conditioning before stem cell transplant will do the trick.
Will see what myelosuppression, bone marrow transplant, and CCR5 antagonism gets us in our upcoming trial. Just wondering if we might need to go one step further to help get rid of that viral reservoir once and for all.
I guess that's the difference between a functional cure and a sterilizing cure, whether HIV remains in the body or not.
Definitely worth a try, and Dr. Sacha must have good reason to think they can eliminate the reservoir while protecting further infection with leronlimab. Or maybe they are saying the reservoir will stay, but will stay suppressed and we are going for a functional cure.
https://www.cell.com/immunity/fulltext/S1074-7613(18)30201-2
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154081/
Myelosuppression prior to bone marrow transplant helps bring the CD4+ T-memory cell reservoir down, but I wonder if it will be enough?
I think any "cure" will need to involve a "kick and kill" type strategy to reactivate the latent virus while protecting new cells (with CCR5 antagonists or CCR5 gene editing / knockout), allowing the immune system to wipe out the viral reservoir while keeping the re-activated virus from spreading.
Have been an investor in SGMO for a while with their efforts at CCR5 KO, and ongoing trials to look at the effects on higher editing (blocking more cells from HIV infection by editing CCR5 out of a higher percentage of immune cells), it has been challenging to keep HIV viral load down with CCR5 knockout. Maybe they just haven't done it well enough, and leronlimab plus myeloablative conditioning before stem cell transplant will do the trick.
Will see what myelosuppression, bone marrow transplant, and CCR5 antagonism gets us in our upcoming trial. Just wondering if we might need to go one step further to help get rid of that viral reservoir once and for all.
I guess that's the difference between a functional cure and a sterilizing cure, whether HIV remains in the body or not.
Definitely worth a try, and Dr. Sacha must have good reason to think they can eliminate the reservoir while protecting further infection with leronlimab. Or maybe they are saying the reservoir will stay, but will stay suppressed and we are going for a functional cure.
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