Highly active antiretroviral therapy (HAART) increases CD4⁺ cell numbers, but its ability to correct the human immunodeficiency virus (HIV)–induced immune deficiency remains unknown. A three-phase T cell reconstitution was demonstrated after HAART, with: (i) an early rise of memory CD4⁺ cells, (ii) a reduction in T cell activation correlated to the decreasing retroviral activity together with an improved CD4⁺ T cell reactivity to recall antigens, and (iii) a late rise of “naı̈ve” CD4⁺ lymphocytes while CD8⁺ T cells declined, however, without complete normalization of these parameters. Thus, decreasing the HIV load can reverse HIV-driven activation and CD4⁺ T cell defects in advanced HIV-infected patients.