That sounds like a problem with the accessibility APIs then. I'd imagine that the script that replaces the DOM in-place also uses History API to tell the browse

That sounds like a problem with the accessibility APIs then. I'd imagine that the script that replaces the DOM in-place also uses History API to tell the browser that this is a new page. At that point the browser should announce that it's a new page and do whatever you've configured it to do, but I just tried it in ChromeVox and it doesn't.