Mitochondrial DNA Decline in T Cells of HIV-1 Seroconverters May Be Dependent on Immune Activation

Background. Earlier reports have indicated that human immunodeficiency virus type 1 (HIV-1) infection itself might cause mitochondrial DNA (mtDNA) decline in peripheral blood mononuclear cells (PBMCs). However, the mtDNA dynamics within this heterogeneous cell population during HIV-1 infection are not fully understood. Methods. mtDNA content was assessed longitudinally in PBMCs and in isolated CD4+ and CD8+ T cells from 16 documented HIV-1 seroconverters who were naive to antiretroviral therapy. The correlation between the mtDNA content of CD4+ and CD8+ T cells and their immunologically activated proportion was studied. Additionally, mtDNA content was measured within isolated activated and nonactivated CD4+ and CD8+ T cells obtained from 5 antiretroviral-naive men with chronic HIV-1 infection. Results. In the seroconverter group, mtDNA content in CD8+ T cells decreased 5 years after seroconversion (P p .007). mtDNA content in either CD4+ or CD8+ T cells did not correlate with the proportion of activated cells within either population. However, for the chronically infected men, mtDNA content in activated CD8+ T cells was lower than that in nonactivated cells ( P p .043). A similar trend was observed in the CD4+ T cell fraction. Conclusions. These findings indicate that HIV-1 infection affects mtDNA content, particularly in the most immunologically activated cells. Furthermore, the importance of measuring mtDNA in specific cell fractions rather than in the heterogeneous PBMC population is emphasized.