DSR and custom resolution downsampling both work with Pillars of Eternity, you just have to set the resolution on your desktop before launching the game (and then select it in-game, if it wasn't already applied).
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Slightly off-topic, but related to rendering weirdness:
At 1920x1080, if you use a zoom range of 0.75 - 1.5, it's slightly annoying to get back to the default zoom level using the mouse wheel if you zoom in by 3 or more levels - you have to zoom out all the way, then back in, or hit the Reset Zoom button.
If you use a zoom range of 0.5 - 1.5, you can get back to the default zoom level after zooming in 3 or more levels using the mouse wheel, but the background is blurred slightly unless you zoom out all the way, then back in, or hit the Reset Zoom button.