Disorders of immune reconstitution in patients with HIV infection responding to antiretroviral therapy

Abstract

Patients with HIV infection who were very immunodeficient before achieving a virologic response to antiretroviral therapy (ART) may experience various disorders of immune reconstitution. Immune restoration disease occurs in approximately 10% to 50% of patients and results from the restoration of a pathogen-specific immune response that causes immunopathology and presents as tissue inflammation or cellular proliferative disease. Opportunistic infections occur in no more than 5% of patients, but approximately one half of these patients have higher than expected CD4 T-cell counts and appear to have residual immune dysfunction. Autoimmune disease may arise because the reconstituted immune system confers an increased susceptibility to immune dysregulation but there may be different mechanisms because Graves' disease presents after a median time of about 2 years of ART whereas systemic lupus erythematosus presents earlier. Persistent CD4 T-cell deficiency (< 500/microL) affects up to 60% of patients and appears to reflect depletion of the naïve T-cell pool that results from low production and/or increased turnover of cells.