Immune restoration and CD4+ T-cell function with antiretroviral therapies

OBJECTIVES: To review the current understanding of the details and mechanisms of immune restoration that follows administration of suppressive antiretroviral therapies to persons with chronic HIV-1 infection. SUMMARY: A first-phase cellular increase often includes increases in multiple circulating lymphocyte populations and is largely attributable to rapid redistribution of cells from lymphoid tissue. A second slower phase is largely comprised of naïve cell increases that may reflect cells newly produced in the thymus. Improvement in CD4+ cell function is demonstrable but functional restoration is incomplete. Immunization can enhance the restoration of CD4+ cell-dependent responses, and the magnitude of restoration is related in part to the degree to which HIV-1 replication and immune activation are controlled. Despite the incomplete nature of immune restoration seen after suppression of HIV-1 replication in chronic infection, clinical benefits of these responses are reflected in decreased HIV-1-related opportunistic infections and mortality. The effects of these therapies on the occurrence of non-Hodgkins lymphoma are less apparent. CONCLUSIONS: Suppression of HIV-1 replication results in both laboratory and clinical evidence of immune restoration. Although incomplete, this immune restoration provides 'breathing room' to develop better-tolerated antiviral therapies and therapies designed to enhance immune function.