SOPHOOS~1.DLL and sophos_detoured.dll

Are you using the on-premise SEC managed client?

Sophos Anti-Virus used to use the AppInit_Dlls key you mention to ensure that the Sophos detours DLL was loaded into processes for the purpose of data control and buffer overflow protection. 

In the Central client at least, this is no longer used, mainly because it doesn't work if Secure boot is enabled.  Now the sophosed.sys driver injects the DLL as processes start.

So in summary, this is something that the Sophos Anti-Virus install used to do but no longer does.  I can only think you must be running an old version of Sophos.

Sophos Endpoint: UEFI and Secure Boot compatible computers prevent Data Control from working details this. What OS are you seeing this on?  Windows 7?

It could absolutely be out of date. It does it about once a month. The OS is Windows Server 2012. I think I will check the updates and see if that is once triggering it. Thank you for the help.

I think 2012 and Windows 7 are the same platform, so it could be that Sophos on that OS still uses the appinit_dlls key which is fine. Unless it's causing an issue?

So currently it is up to date. SOPHOS~1 ran twice this month on the device but our other security tool only reported it as malicious once. I will keep researching.

No issues just researching to see if this was malicious as reported or was a false alarm. I am leaning to false alarm but wanted to provide better info on why.

Well the keys you mention are only added by the Sophos Anti-Virus installer at install.  When Sophos performs a major update, it might uninstall and re-install which could cause it to remove and re-add the keys.  This wouldn't happen more than once a month.  It is all expected.