Primary HIV-1 infection refers to the events surrounding the acquisition of HIV-1 infection. It is commonly associated with a nonspecific clinical syndrome that occurs within 2 to 4 weeks after exposure in 40% to 90% of persons acquiring HIV-1. Patients identified prior to seroconversion often have plasma titers in excess of 500,000 copies/mL. Over time, plasma HIV-1 RNA titers decrease and eventually reach a "set point." Treatment of primary HIV-1 infection with highly active antiretroviral therapy does not prevent establishment of chronic infection. However, it potentially may decrease the viral set point, prevent evolution of resistant mutants, preserve immune function, improve clinical outcome, and possibly allow for viral control after withdrawal of antiretroviral therapy. Transmission of viral strains with decreased susceptibility to antiviral drugs increases the difficulty of choosing an antiretroviral regimen. Other medications, including immunomodulators, are under study as adjuvant therapy for treatment of primary HIV-1 infection.