Evasion of cytotoxic T lymphocytes is a major driving force of HIV-1 evolution within a host. In a genetically homogenous population where some MHC class I types are dominant, repeated selection of escape mutants can cause HIV-1 to lose fitness. However, in a heterogenous population, reversions are more frequent and attenuation of HIV is slower. HIV-1 may have experienced adaptation to the human host after crossing species from primates, but immune selection and random drift are causing the viral genome to degenerate. Antiviral therapy further cuts into viral fitness, even when the drugs are resisted. HIV-1 is an important example which shows that genetic entropy is operating throughout the biological realm, even while meaningful genetic adaptations are occurring.