Is there a role for immunotherapy in controlling HIV infection?

Although HAART restores immune function in patients with HIV infection, restoration is incomplete. Functional restoration is seen primarily in responses to antigens that are prevalent in HIV-infected persons. Immunization is required to restore responses to antigens that are not predictably present. As an exception, HIV-specific responses are also generally not restored despite the prevalence of these antigens. This may be because HIV replication specifically targets and either destroys or renders nonfunctional HIV-reactive CD4+ T cells. Perhaps because HIV selectively targets HIV-reactive immune cells, therapeutic immunization strategies are particularly important areas of investigation in the treatment of HIV disease. Strategies designed to restore HIV-specific CD4+ T-cell function must also enhance the activity of HIV-specific cytolytic T cells, since these are the likely key mediators of defense against HIV replication. Both active immunization strategies and treatment interruption strategies may enhance HIV-specific immune responses. Treatment interruption, by increasing exposure to HIV antigens through heightened HIV replication, also runs the risk of permitting sufficient HIV replication to damage HIV-responsive CD4+ cells as well as enhancing the losses of other CD4+ cell populations that may protect against opportunistic complications of HIV disease. Thus, treatment interruption strategies require careful and sophisticated monitoring and should not be tried at home.