Reply from finesand, who is out of posts. BTW, I got a premium upgrade for free, I believe they private messeged me a few days after joining saying I was upgraded.
finesand’s reply:
my first paper quote was co-authored by NP - so he surely knows about IC90 lol.
The 700mg results have proven and resolved the issue,
but what one might like to see is the occupancy percentage.
They surely measure it as shown in the paper and hopefully will show IC90 in the next mono paper (CROI'19)! They already knew about the dosage and IC90 correlation..
Dhody et al. emphasize a IC90 variation between viral rebound and responsive groups[26]:
Also note the Thompson's reference to half-life and occupancy ..
What CYDY should do (and we even told them via email!) is
to determine the amount of PRO140 via SC to coat/occupy all CCR5 .. for X days
under certain circumstances, depending on body weight and immune system.
However, since all other causes have been excluded
for the VL rebound (tropism change or resistance) and other experts already
opined to increase the dosage (b/c that is it) .. we should be fine now.
But if 342mg half-life lasted 3.7 days, 700mg should be good enough for a week half-life.
5mg/kg IV -> 500mg/100kg IV patient, so 4x 700mg should also suffice
more than enough one would think.
Back in June 2018 when we received Thompson's opinion paper we did quite some DD on the whole VL rebound issue.
The 700mg results were very satisfying and relieving - even though, SP wasn't yet able to respond.
finesand’s reply:
my first paper quote was co-authored by NP - so he surely knows about IC90 lol.
The 700mg results have proven and resolved the issue,
but what one might like to see is the occupancy percentage.
They surely measure it as shown in the paper and hopefully will show IC90 in the next mono paper (CROI'19)! They already knew about the dosage and IC90 correlation..
Dhody et al. emphasize a IC90 variation between viral rebound and responsive groups[26]:
Quote:However, there was a noted difference in the IC90 values from virologic rebound (10.8+/−9.28) and non virologic rebound (6.7+/−6.groups on entry analysis indicating that more PRO 140 was required to reach IC90 by the group that was destined to rebound on PRO 140 monotherapy.
Also note the Thompson's reference to half-life and occupancy ..
Quote:The mean terminal half-life of PRO 140 after a single
intravenous dose ranged from 3.1 to 3.9 days
[14,17]. After multiple subcutaneous doses of PRO
140, mean terminal half-life was 3.4 and 3.7 days at
162 and 342 mg, respectively [18]. At a single intra-
venous dose of 5 mg/kg, PRO 140, CCR5 receptor
coating was observed for more than 60 days [19].
What CYDY should do (and we even told them via email!) is
to determine the amount of PRO140 via SC to coat/occupy all CCR5 .. for X days
under certain circumstances, depending on body weight and immune system.
However, since all other causes have been excluded
for the VL rebound (tropism change or resistance) and other experts already
opined to increase the dosage (b/c that is it) .. we should be fine now.
But if 342mg half-life lasted 3.7 days, 700mg should be good enough for a week half-life.
5mg/kg IV -> 500mg/100kg IV patient, so 4x 700mg should also suffice
more than enough one would think.
Back in June 2018 when we received Thompson's opinion paper we did quite some DD on the whole VL rebound issue.
The 700mg results were very satisfying and relieving - even though, SP wasn't yet able to respond.
