No abstract

After long-term anti-retroviral therapy (ART) treatment, most human immunodeficiency virus (HIV)/Acquired Immure Deficiency Syndrome (AIDS) patients can achieve virological suppression and gradual recovery of CD4+ T-lymphocyte (CD4+ T cell) counts. However, some patients still fail to attain normal CD4+ T cell counts; this group of patients are called immune non-responders (INRs), and these patients show severe immune dysfunction. The potential mechanism of poor immune reconstitution (PIR) remains unclear and the identification of uniform biomarkers to predict the occurrence of PIR is particularly vital. But limited information is available on the relationship between circulating markers of INRs and immune recovery. Hence, this review summarises alterations in the intestine microbiota and associated markers in the setting of PIR to better understand host-microbiota-metabolite interactions in HIV immune reconstitution and to identify biomarkers that can predict recovery of CD4+ T cell counts in INRs.

Background Highly active anti-retroviral therapy (HAART) can successfully suppress human immunodeficiency virus (HIV) viral replication and reconstruct immune function reconstruction in HIV-1-infected patients. However, about 15–30% of HIV-1-infected patients still fail to recover their CD4+ T cell counts after HAART treatment, which means immune reconstruction failure. Pyroptosis plays an important role in the death of CD4+ T cells in HIV-1- infected patients. The study aims to explore the association between the expression of pyroptosis in peripheral blood and immune function reconstruction in HIV-1- infected patients. Methods One hundred thirty-five HIV-1-infected patients including immunological non-responders (INR) group, immunological responders (IR) group and normal immune function control (NC) group were analyzed. The expression of GSDMD and Caspase-1 in peripheral blood of HIV-1-infected patients were measured by qPCR. The concentrations of GSDMD, Caspase-1, IL-1β and IL-18 in the peripheral serum were quantified by ELISA. The associations between the expression of pyroptosis in peripheral blood and immune function reconstruction were analyzed using multivariate logistic models. Results The relative expression of GSDMD mRNA and caspase-1 mRNA in peripheral blood, as well as the expression of IL-18 cytokine in the INR, were significantly higher than those in the IR and NC (P < 0.05). There was no significant difference in the expression of IL-1β cytokine (P > 0.05). Multivariate logistic analysis showed that the patients with baseline CD4+ T cell counts less than 100 cells/μL (aOR 7.051, 95% CI 1.115–44.592, P = 0.038), high level of expression of Caspase-1mRNA (aOR 2.803, 95% CI 1.065–7.377, P = 0.037) and IL-18 cytokine (aOR 10.131, 95% CI 1.616–63.505, P = 0.013) had significant poor CD4+ T cell recovery. Conclusions The baseline CD4+ T cell counts less than 100 cells/μL, high relative expression of Caspase-1 mRNA, and high expression of IL-18 cytokine are associated factors that affect the reconstruction of immune function.