It sounds like he has something which is not allowing him to do anything until he gets both ComboFix and HiJackthis! running in safe mode. Is safe mode itself being blocked?

I hate to mention such a drastic step, but you might want to try and backup your most crucial files and reformat the affected drive.

I had something similar happen not too long ago (it did not need a reformat), bu it was quite odd in how it unfolded. I left my computer on while going to watch Heroes, no torrents or files downloading, no connections open except for Firefox, and within the hour, something had rebooted and infected my computer. Logged back on, thinking it was just my screensaver that triggered the login screen, and I was treated to "buy Antivirus 2009 now!" shit. Most webpages were blocked, Avast wouldn't start, but somehow, I got Combofix (from another computer I think), and cleared everything up. Killed my whole night, but otherwise a clean system.

Maybe this is similar to what you have?