Association of cell free mitochondrial DNA and caspase-1 expression with disease severity and ARTs efficacy in HIV infection.

ABSTRACT

HIV infection is a global health concern. Current HIV-diagnostics provide information about the disease progression and efficacy of anti-retroviral therapies (ARVs), but this information is very limited and sometimes imprecise. Present study assessed the potential role of mononuclear cell (MNC) death, expression of caspases (1&3) and cell free mitochondrial DNA (CF mt-DNA) in HIV infected individuals. Apoptosis, cell-count, expression of caspases and CF mt-DNA were measured through flow cytometry and qPCR, respectively, in HIV infected individuals (n = 120) divided in two groups i.e. ARVs-receiving (treated, n = 87), ART-naïve (untreated, n = 37) and healthy individuals (n = 47). Data showed significant (p < 0.0001) cell death in untreated individuals than treated and healthy individuals. CD4-positive T-cell percentage declined (p < 0.0001) in untreated as compared to treated individuals. Caspase-1, an indicator of pyroptosis, and CF mt-DNA were also elevated in untreated HIV infected individuals. Untreated individuals when administered with ARVs showed improved CD4-positive T-cell percentage, lower caspase-1, CF mt-DNA and cell death. Data elucidated positive co-relation between cell death and CF mt-DNA in treated and untreated HIV infected individuals. While CD4-positive T-cell percentage was negatively correlated with caspase-1 expression and CF mt-DNA. Elevated levels of CF mt-DNA and caspase-1 in HIV infected individuals, positive correlation between cell death and CF mt-DNA, negative correlation of CD4-positive T-cell percentage with CF mt-DNA and caspase-1 expression clearly indicated the potential of CF mt-DNA and caspase-1 as a novel disease progression and ARTs effectiveness biomarkers in HIV.