In this short review, clinical manifestations associated with primary HIV infection (PHI) and their impact on progression to AIDS will be described. High levels of viral replication of viruses with a restricted heterogeneity and decreased CD4/CD8 cell ratio are hallmarks of PHI. Within weeks to months following PHI, a marked decrease in viremia and an increase of CD4 cells which stabilise at levels below normal values occur. Early decrease of viremia to low levels, low proviral levels, stabilisation of CD4 cells to values close to the normal range postpone the development of AIDS. Tentative goal of early antiviral therapy in PHI might be, by decreasing viral load, to restore CD4 cell levels to normal value and to transform the majority of PHI patients into long-term non-progressors. Selection of therapeutic regimens, duration of antiviral treatment and validation of appropriate virological and immunological markers are the key issues in the context of PHI treatment. These issues and the results of therapeutic interventions with mono and bitherapy in PHI as well as combined drug regimens for future studies are presented and discussed.