Epidemiologists have long established beyond all reasonable doubt that infection by the human immunodeficiency virus type 1 (HIV-1) leads to the acquired immune deficiency syndrome (AIDS). Natural history cohorts have demonstrated that the median time from infection to development of AIDS is approximately 12 years, and that this long duration is broadly similar in all populations infected by HIV-1, in all risk groups, in all ethnic groups and in all geographical areas. These epidemiological observations suggest that HIV-1 causes AIDS largely independently of human major histocompatibility complex (MHC) and HIV-1 sequence polymorphisms, as great diversity of both these factors exist world-wide. This is not to say that HLA and HIV diversity do not affect the natural history of HIV disease, but these observations support a common mechanism of HIV-1 pathogenesis which is largely independent of human and viral diversity.