I think the core issue with the reaction isn't the effect itself. It's more an imbalance between your health (which has no natural growth) and their base numbers, that do. Towards the end of the run enemies have 10k+ poison per application. And I'm applying shield as often as the internal cooldown of charge will allow, same with regen usually. So I technically have the regen/heal/whatever to keep up with the DPS of those poison applications just fine. It's just that a single tick instantly kills me from full health. Since even with taking +100 health every single upgrade after you get 1s CD on your core. You still only have about 4.5k hp at that point, and it doesn't take a lot of triggers before each tick of poison deals more than that. Enemies also have HP in the millions at that point. So as strong as my attacks are, it still takes a couple seconds to chew through that.
Another option is to make regen and poison work the way I seem to recall it working in The Bazaar. Where if you have say 1100 poison and 1000 regen. It just makes you have 100 poison effectively. So unless you out-poison the regen, you can never kill with poison. That would make this solve-able as long as you have enough regen scaling. But it might also make it so you literally cannot lose.
Edit: Made it to 65, but died to the poison on shield counter again. I tried to purposefully remove my shielder from my charge loop to make it go slower, and only upgraded the CD to where it would go before shadow assassin. But eventually that was still enough to make the counter one-shot me before I could eat through the 1.5-2m worth of hp they have.