Increased Levels of Caspase-1 and IL-1β Among Adults With Persistent Immune Activation After 12 Years of Suppressive Antiretroviral Therapy in the Infectious Diseases Institute HIV Treatment Cohort

Abstract

Abstract Background We sought evidence of activated pyroptosis and the inflammasome pathways among human immunodeficiency virus (HIV)–infected adults after 12 years of suppressive antiretroviral therapy (ART) and persistent immune activation in the Infectious Diseases Institute HIV treatment cohort in Uganda. Methods In a cross-sectional study, using peripheral blood mononuclear cells of HIV-infected individuals with high and low immune activation (CD4/CD8+CD38+HLA-DR+ cells) relative to HIV-negative reference group, caspase-1 expression was measured using flow cytometry and plasma interleukin 18 and interleukin 1β (IL-1β) levels using enzyme-linked immunosorbent assay. Results There was higher expression of caspase-1 by CD4 T cells of ART-treated individuals with high immune activation relative to those with lower immune activation (P = .04). Similarly, plasma levels of IL-1β were higher among ART-treated individuals with high immune activation levels relative to those with low immune activation levels (P = .009). We observed a low positive correlation between caspase-1 expression by CD4/CD8 T cells and immune activation levels (r  = 0.497 and r  = 0.329, respectively). Conclusions Caspase-1 and IL-1β were high among individuals with high immune activation despite 12 years of suppressive ART. There is a need to further understand the role of persistent abortive infection and the latent HIV reservoir characteristics as drivers of persistent activation and inflammation and to subsequently intervene to prevent the complications of chronic immune activation during long-term ART.