As far as I can tell, yes. At least they can be modified in the GUI, whereas the dialogue subs are somehow greyed out and don't react to mouse clicks at all. edit: Let me rephrase that. The option for dialoge subs is no more greyed out as all the others when not selected, but other than the others, it doesn't light up when I try to select it by mouse or cursor keys. I'll try that after work, thanks!

Editing the config file did the trick. However, the option still can't be changed in-game. Now, it stays on ON and is still not changeable. (?)

This'll work for now, thanks! On the long run, I would like to know what causes this bug and if it can be fixed by the player somehow. I also would like to change the setting on the fly sometimes, to play without subs most of the time and enable them only for dialogue that's hard to understand.

It's very strange that this affects only this one particular option.

You're welcome. Glad of having helped you. Enjoy the game.

Speaking of the issue, the only cause I can think of is that the game has not the sufficient rights to edit the config files, but this doesn't explain why the issue is exclusively related to the subtitle settings.

Indeed, and I did install it normally via the "offline" installer, i.e. without Galaxy. Also, I didn't mess with any files in its installation folder until I applied your solution.

For anyone else who stumbles across this with the same issue:

Run BioshockHD.exe as administrator, your options will not only work as designed but will actually save and persist when you select them.