I just generated an offer from Carmax and set an appointment for Wednesday. My Title is in both my name and my wife's. Does she have to sign and if so, does she have to be presented when signing? She is semi-invalid and somewhat confined to home.

Yes, all owners on title must sign. I would ask but in all my transactions they witness the signatures.

Yes both people will need to be present

Carmax makes everyone sign and in person for whoever is on the title. But, depending on the circumstance, I can imagine they'd work with you and find a way since ,at the end of the day, they want your business. I don't work at carmax, just familiar with the process from previous transactions.