Key renegotiation essentially means agreeing on a new session-key. To do this both parties needs to be sure the other-end is the real other party and not some mallory trying to impersonate the party.
The only way to do this, is using the "secret" from the other end. When you have a "running" openvpn-session, it does not matter anymore which way of authentication is used. This comes back to you when you need to renegotiate.
When you are using certificates, the private-key is accessed to do this. When openvpn is not caching passwords, you will be asked for the private-key password.
Renegotiating client's using 2-factor-authentication requires the server to revalidate the client and therefore it's "secret" is needed and the client is asked for a new OTP.
I can image this is annoying for the user. You could try to increase the renegotiation-time to something acceptable period, like 4 hours:
reneg-sec 14400
but take care of the other crypto-settings, as longer session-keys may have other security issues, depending on your situation.
Probably you are allready using different client-configs for 2-factor and certs, so you might consider to use different openvpn-daemons to finetune for both setups.