"Researchers have offered a mathematical model based on the changing demography of Europe from 1000 to 1800 AD demonstrating how plague epidemics, 1347 to 1670, could have provided the selection pressure that raised the frequency of a mutation to the level seen today that prevent HIV from entering macrophages that carry the mutation (the average frequency of this allele is 10% in European populations).[9] It is suggested that the original single mutation appeared over 2,500 years ago and that persistent epidemics of a haemorrhagic fever struck at the early classical civilizations."