Immunopathogenesis of asymptomatic chronic HIV Infection: the calm before the storm

Abstract

HIV and pathogenic simian immunodeficiency virus infection are characterized by chronic immune activation. This review addresses the factors that influence immune activation and may thus determine the rate of disease progression during the asymptomatic period of HIV. Immune activation stems from foreign antigen stimulation, including HIV, microbial products and coinfections and compensatory homeostatic mechanisms. Continuous immune stimulation creates a permissive environment for further viral replication, while temporarily allowing successful replenishment of the T-cell pool. Type I interferon, microbial translocation, activated (but ineffective) effector T cells, unruly regulatory T cells and inadequate T helper 17 cells all play important roles in the cycle of activation, functional exhaustion and T-cell death that leads to immunodeficiency. The asymptomatic chronic phase of HIV infection is a dynamic balance between host and virus, the outcome of which determines an individual's course of disease. Evaluation of the factors that determine the immunologic threshold of disease progression could assist in designing therapeutic strategies, including individualized timing of ART.