Symptomatic primary human immunodeficiency virus (HIV) infection was originally defined as a mononucleosis-like syndrome, with or without lymphocytic meningitis, associated with seroconversion for HIV. However, other protean clinical manifestations have been reported, and diagnosis should be considered in patients with risk factors for HIV who experience acute infectious illness, requiring search for p24 antigenemia and development of HIV antibodies. The clinical presentation of symptomatic HIV infection could predict the subsequent disease progression. In several studies, it is associated with poor prognosis. Pathogenesis relies on the host immune response and on virologic parameters. Early antiretroviral therapy on acute HIV infection could modify the course of infection.