The human immunodeficiency virus (HIV) is unique in its capacity to produce chronic disease in almost all infected hosts. To accomplish this, it has evolved multiple mechanisms to effectively evade the immune response. HIV encodes at least one protein that makes infected cells resistant to CTL killing by downmodulating epitope (peptide plus MHC-I protein) density on the infected cell surface. In addition, HIV encodes several mechanisms to promote apoptosis of HIV-specific CTLs. The end result is that infected cells have a reduced susceptibility to CTLs, survive longer and produce more viral antigenic variants that can further evade the immune response.