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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. |
