We like specific info here so we can be as accurate as possible for you. But...I-75 just over the Ohio river is a long up hill that's pretty gradual and no big deal. Most of KY is not terribly twisty turny or hilly except just before you get to the border of TN it gets mildly hilly, again nothing you can't handle.
I-40 west bound out of Asheville you run into the Pigeon River Gorge that is very twisty turny and hilly with some fair down hill grades. Semi trucks are relegated to the outside lane and speed limit of 55. I just fall in with them and leave a good following gap and go with the flow with no problem. There is no way that is any better to go around it so that's what you got. Its a beautiful drive though.
West bound I-40 isn't bad either. If you are going to Crossville then you will have a good climb up to the Cumberland Plateau, still not terrible but you will have to push on the gas pedal.
I advise against going through the Nat'l Park (441) through New Found Gap pulling a trailer. That is steep both up and down with lots of turns, some sharp and tight. With not having any experience pulling in the mountains you should not attempt it. I see everything from truck campers, class C's, MoHo's and travel trailers with over heated brakes every time I go through there.
