Activated/Cycling Treg Deficiency and Mitochondrial Alterations in Immunological Non-Responders to Antiretroviral Therapy.

Background: Regulatory T-cells (Tregs) play a crucial role in maintaining immune homeostasis, but their dynamics are altered in a subset of people living with Human Immunodeficiency Virus (HIV) known as immunological non-responders (INRs). INRs fail to reconstitute CD4 T-cell counts despite viral suppression. This study aimed to examine Treg dysregulation in INRs, comparing them to immunological responders (IRs) and healthy controls (HCs).

In HIV-Infected Immunological Non-Responders, Hepatitis C Virus Eradication Contributes to Incomplete Normalization of Systemic Inflammation Indexes, but Does Not Lead to Rapid CD4+ T-Cell Count Recovery.

In HIV-positive individuals taking antiretroviral therapy, coinfection with hepatitis C virus (HCV) increases systemic inflammation, which interferes with the CD4 T-cells regeneration. This study evaluated the effect of HCV eradication on systemic inflammation and CD4 T-cell regeneration in patients who gave poor response to antiretroviral therapy, the so-called "immunological non-responders" (INRs). HIV-infected patients who received a course of direct-acting antivirals for treating hepatitis C were examined.

Gut-derived bacterial toxins impair memory CD4+ T cell mitochondrial function in HIV-1 infection.

People living with HIV (PLWH) who are immune nonresponders (INRs) are at greater risk of comorbidity and mortality than are immune responders (IRs) who restore their CD4+ T cell count after antiretroviral therapy (ART). INRs have low CD4+ T cell counts (<350 c/μL), heightened systemic inflammation, and increased CD4+ T cell cycling (Ki67+). Here, we report the findings that memory CD4+ T cells and plasma samples of INRs from several cohorts are enriched in gut-derived bacterial solutes p-cresol sulfate (PCS) and indoxyl sulfate (IS) that both negatively correlated with CD4+ T cell counts.

Metabolic Features of Activated Memory CD4 T-Cells Derived from HIV-Infected Immunological Non-responders to Highly Active Antiretroviral Therapy.

Immunological non-responders (INR) are HIV-infected subjects that fail to restore CD4 T-cell counts despite undetectable HIV viral load, which is controlled by highly active antiretroviral therapy (HAART). In INR, impaired immune restoration is linked to low-productive proliferation of memory CD4 T-lymphocytes. Taking into account that T-cell ability to divide depends on the activity of metabolic pathways, we aimed to determine rates of mitochondrial respiration and glycolysis in memory CD4 T-cells of INR.

Changes in the Regulatory T-Lymphocyte Counts in HIV-Infected Patients with a Discordant Response to Antiretroviral Therapy.

We examined HIV-infected patients with different efficacies of immune system restoration during antiretroviral therapy. The study showed that against the background of low CD4+ T cell counts, subjects with a discordant immunologic response (patients with <350 CD4 T cells per μL of blood after more than two years of treatment) develop a regulatory CD4 T cell (T) deficiency. Furthermore, in these patients, the immunodeficiency is accompanied by an increase in the T frequency.