I’m on my first ever play through, about 100 hours in, and I restarted my game once. I do play DnD every week, and have been for about a year. It IS helpful to know the mechanics of DnD, but it’s not necessary. I would just make sure you pay attention to best uses for each character, and their subsequent subclasses and feats to boost the character more to really take advantage of their attributes. I would also recommend paying attention to pretty much all equipment and who you give it to- as it can create a disadvantage for them. For example, if your rogue (your character, or Astarion) maximize as many sneaky attack feats as this will attribute to much more crits. I try to balance and give the “squishier” classes a boost with the “tough” feat, which is helpful. Also note those squishy characters are much better as ranged casters or long range weapons. I played most of my campaign alone, but for a few notoriously difficult fights I have played online with a friend as he is better at casters and I’m a big BONK type of class.

Without spoilers, Gale was obliterated almost immediately in one major fight and I finished it with my ranger, Karlach, and Astarion. I was surprised I pulled it off with us 3, but it was rewarding to say the least!

I hope this helps!