CD4 cell counts in human immunodeficiency virus (HIV)-infected patients increase under effective highly active antiretroviral therapy (HAART). Similar kinetics of response is observed irrespective of the stage of infection in which HAART is initiated. An early rise in memory cells is followed by a gradual and continual rise in naive cells, which reflects ongoing thymic production and these cells exhibit rediversification of the CD4 T cell repertoire damaged during HIV-1 infection. Studies in patients receiving HAART indicate that the responsiveness of memory CD4 T cells to opportunistic pathogens is restored. Although response to rare antigens or HIV-1 is generally not preserved in patients initiating HAART during established infection, the ability to detect Th1 response in vitro indicates that antigen-specific cells are not completely depleted in many cases. Strong response of tetanus toxoid-specific cells after administration of tetanus toxoid vaccine and strong HIV-1 p24-specific response after the re-exposure to viral antigen because of treatment interruption have been observed in the context of effective therapy initiated during advanced infection. These findings suggest that long-term immune recovery is feasible when HAART is given during chronic infection and might require immune intervention in addition to stable virus control.