A fairly extreme measure for a failed driver install but one of the things you can try is restoring to a recent restore point (if you have one) before you first updated the Line6 driver. It could be you have a bad registry entry. Here is a really good link on the (Code 39) error you are getting: I have opened a support ticket, though I would still very much appreciate any other suggestions. Not sure what set of processes would be "unnecessary" -) I'll try with defender turned off to no avail (though I would have expected a message or something if it intervened). I've had nothing plugged in to the USB port for this. I've also downloaded the driver a number of times, with various browsers to avoid anything IE specific (like issues with signing). Unfortunately, I've done almost all of them already to no avail. Thanks for the suggestions, HonestOpinion. This may include going into the Task Manager and killing unnecessary processes. Have you tried loading the driver with your anti-virus software turned off including Windows 10's Defender? You might also try unplugging anything else in the USB ports and disabling every unnecessary process running on the PC for the duration of the driver install. Continue to uninstall the driver first before any attempts to reload it. One approach you may have already tried is right clicking on the driver in Device Manager and attempting to update it from the list of local drivers already on your machine (rather than updating from online). Get a fresh download of the correct driver. If the above does not work and given your familiarity with Windows and former employment with Microsoft these may all be things you have tried already but here goes.
Reinstalling the correct version of HX Edit for your OS is the easiest way to guarantee you are getting the correct driver for your OS. It sounds like you are getting either the wrong device driver or your device driver is getting corrupted in the download process somehow judging by the error message (but not necessarily). I would definitely start with an uninstall of the driver and Helix software from the Windows 10 "Control Panel -> Programs and Features" and then reboot the PC, and do a fresh download of HX Edit from Line6 which will include the latest driver.