Virulence is relative capacity of a virus, compared to other closely related viruses, to produce disease in a host. Viral strains considered as virulent have been described in HIV-1 infected patients. They are characterized in vitro by enhanced cellular host range, rapid kinetic of replication and increased capacity of syncytium induction. Some genetic modification of the V3 loop in the envelope gene have been associated with the emergence of these strains. But at AIDS diagnosis, and even at the terminal stage of AIDS, only about half of the patients harbour syncytium inducing variants. There are much evidence for continuous viral replication throughout all stages of HIV-1 infection. There is no viral latency state in the natural HIV infection. This increasing viral burden might have a pivotal role in the pathogenesis of HIV disease. HIV-2 is less pathogenic than HIV-1. The nature of the viral determinants responsible for this reduced virulence remains unknown. In the simian immunodeficiency virus model, virulent and avirulent strains have been described and the nef gene seems to have a critical role in pathogenicity.