I heard many good things about it so what I want to ask is, do I have to use anything in order for it to work? like SKSE or Bash or do I only have to put it last in the load order and that's it?

2) Will Automatic Variants.esp be affected if its loaded after it?

3) Will it make the gameplay too hard and force me to use followers?

This should probably be in the ASIS thread. You have to run the patcher file, then put it last in the load order and the Dependency file second last. There are various options in the patcher.
Don't know about AV.
Personally, I haven't found it to be too hard as it's mostly lower level enemies. I don't need followers. But then I play on adept, so...