The immune response against HIV does not result in complete viral clearance. Recent interventions have focused on novel strategies to modify human anti-HIV immunity. Active vaccination of patients with HIV infection (vaccine therapy) safely alters the immune repertoire against HIV. This unique approach will provide insight into the immunoregulatory consequences of HIV-specific innate and adaptive immune responses, and hopefully define the immunological Achilles heel of HIV. Once defined, researchers, aided by current biotechnological techniques, can rationally design future vaccines and immune based therapeutic products.