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.

Cycling CD4+ T cells in HIV-infected immune nonresponders have mitochondrial dysfunction.

Immune nonresponder (INR) HIV-1-infected subjects are characterized by their inability to reconstitute the CD4+ T cell pool after antiretroviral therapy. This is linked to poor clinical outcome. Mechanisms underlying immune reconstitution failure are poorly understood, although, counterintuitively, INRs often have increased frequencies of circulating CD4+ T cells in the cell cycle.

Lymphopenia-induced proliferation of CD4 T-cells is associated with CD4 T-lymphocyte exhaustion in treated HIV-infected patients.

Background & Objectives: Under the lymphopenic condition, T-cells divide to maintain their peripheral pool size. Profound chronic lymphopenia in some treated HIV-infected patients, characterized by poor T-cell recovery, might result in intensive homeostatic proliferation and can cause T-cell exhaustion and/or senescence. The present study was undertaken to evaluate the homeostatic proliferation of CD4T-cells in treated HIV-infected individuals, and to determine the amount of phenotypically exhausted and senescent CD4 T-lymphocytes.

Systemic activation of the immune system in HIV infection: The role of the immune complexes (hypothesis).

Currently, immune activation is proven to be the basis for the HIV infection pathogenesis and a strong predictor of the disease progression. Among the causes of systemic immune activation the virus and its products, related infectious agents, pro-inflammatory cytokines, and regulatory CD4+ T cells' decrease are considered. Recently microbial translocation (bacterial products yield into the bloodstream as a result of the gastrointestinal tract mucosal barrier integrity damage) became the most popular hypothesis.

Influence of hepatitis C virus coinfection on CD4⁺ T cells of HIV-infected patients receiving HAART.

Objective: The effects of hepatitis C virus (HCV) coinfection on immune homeostasis and immune restoration in treated HIV infection are not well understood.

Methods: We studied 79 HIV-infected patients who had been receiving HAART for more than 2 years and who had HIV viral load below 50 copies/ml. Four patient groups were studied: HIV/HCV, CD4⁺ cells above 350/μl; HIV/HCV, CD4 cells below 350/μl; HIV/HCV, CD4 cells above 350/μl; HIV/HCV, CD4⁺ cells below 350/μl.