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.