I also have had this problem with Global Hosts, which only began in the last month or two. I am running Vista Home Premium with the current MS updates.
In the past Spy Sweeper has blocked immunization updates, so I routinely shut it down before performing Spybot updates, and that procedure had worked perfectly. With the recent problem I thought that perhaps another AS or AV application was responsible for the difficulty. Accordingly I also shut down Norton Internet Security and Windows Defender, the only other apps with active protection features, but doing so did not fix the problem.
As suggested, I ran Spybot as an administrator, but that did not work.
Fortunately running in Safe mode did work, but this is a bit of a kluge. Is there a more convenient solution?
Thanks for your input on this problem.