Analyses of Mitochondrial DNA and Immune Phenotyping Suggest Accelerated T-Cell Turnover in Treated HIV.

Background: HIV infection is associated with premature aging, and mitochondrial integrity is compromised during the aging process. Because mitochondrial toxicity is a consequence of antiretroviral therapies (ARTs), we hypothesized HIV and long-term ART would correlate with immunosenescence and mitochondrial DNA (mtDNA) pathology.

Methods: Peripheral blood T-cells were immunophenotyped to measure immune activation, proliferation, and immunosenescence in subsets. mtDNA copies per cell and the relative abundance of mtDNA carrying the "common deletion" (RACD) were quantified by droplet digital polymerase chain reaction.

Results: Immune activation was higher in HIV-infected individuals than HIV-uninfected individuals in mature CD4 T-cell subsets (CD4TTM P = 0.025, CD4TEM P = 0.0020) regardless of ART duration. Cell populations from uninfected individuals were more likely to be more senescent populations in mature CD4 T-cell subsets (TTM P = 0.017), and CD8 (CD8TEMRA+ P = 0.0026). No differences were observed in mtDNA or RACD levels in any CD4 T-cell subsets, while CD8TSCM of infected individuals trended to have more mtDNA (P = 0.057) and reduced RACD (P = 0.0025).

Conclusion: Immune activation was higher in HIV-infected individuals than HIV-uninfected individuals in mature CD4 T-cell subsets (CD4TTM P = 0.025, CD4TEM P = 0.0020) regardless of ART duration. Cell populations from uninfected individuals were more likely to be more senescent populations in mature CD4 T-cell subsets (TTM P = 0.017), and CD8 (CD8TEMRA+ P = 0.0026). No differences were observed in mtDNA or RACD levels in any CD4 T-cell subsets, while CD8TSCM of infected individuals trended to have more mtDNA (P = 0.057) and reduced RACD (P = 0.0025).