HIV-1 infection is characterised by persistent viraemia and a progressive decline in both number and function of CD4 T-helper lymphocytes. The inability to contain viral replication presumably results from the lack of an effective HIV-1-specific immune response observed in most HIV-infected individuals. The persistent viraemia and decline in the number and function of CD4 cells lead to a further loss of immunity to HIV-1 as well as to opportunistic pathogens. Highly active antiretroviral therapy (HARRT) has been shown to reconstitute pathogen-specific immune responses in a majority of subjects, with a dramatic drop in the morbidity and mortality caused by opportunistic infections. By contrast, HIV-1-specific immunity remains largely ineffective and most people with chronic HIV-1 infection cannot control viraemia after interruption of HARRT, indicating a need to develop new strategies to maintain and improve HIV-1-specific immunity. Here we review the relative role of CD4 T-helper cells in the immune response against HIV infection and their contribution to cell-mediated immune responses to other pathogens infecting people with AIDS. In addition, we discuss the concepts of: supervised treatment interruptions, therapeutic and preventive vaccination, optimisation of antigen presentation and T-cell priming by ex vivo stimulated and expanded dendritic cells.