Background:  We recently confirmed depletion of mitochondrial DNA (mtDNA) in peripheral blood mononuclear cells (PBMC) from HIV-infected patients naïve to ART, and not only patients exposed to nucleoside reverse transcriptase inhibitors (NRTI). We here assessed whether mtDNA in PBMC reflects the mitochondrial status in organ-specific tissues like skeletal muscles.

Methods:  We included 3 groups:  HIV⁺ NRTI⁺ (n = 24), HIV⁺ ART-naïve (n = 10), and HIV^­ controls (n = 11). Muscle biopsies were examined for:  mtDNA and nuclear (n) DNA using TaqMan real-time polymerase chain reaction (PCR) system; mtDNA deletions using long expands PCR with subsequent gel electrophoresis; and mitochondrial dysfunction expressed as a fraction of cytochrome C-oxidase (COX)-negative muscle fibres. PBMC were examined for mtDNA content using TaqMan real-time PCR system. Nonparametric statistics were used throughout (Mann Whitney and Spearman Rank correlation coefficient). Data are presented as median values and interquartile range.

Results:  MtDNA in PBMC was reduced in both HIV⁺ ART-naïve patients (74, 49 to 117 mtDNA/cell) and HIV⁺ NRTI⁺ (55, 33 to 110) compared to HIV^­ controls (153, 132 to 173) (p <0.01). MtDNA in muscle was reduced in HIV⁺ NRTI⁺ (1281 mt/n DNA ratio, 952 to 1578) compared to HIV^­ controls (1927, 1563 to 2443) (p = 0.03). Furthermore, mtDNA deletions in muscle were more frequent among HIV⁺ NRTI⁺ than both HIV^­controls (p = 0.009) and HIV⁺ ART-naïve patients (p = 0.005). HIV⁺ NRTI⁺ also had a higher fraction of COX-negative fibres than HIV^­ controls (p = 0.04) and possibly more than treatment-naïve patients (^p = 0.09). Neither mtDNA content nor deletions in muscle were correlated with mtDNA in PBMC.

Conclusions:  In skeletal muscle HIV⁺ NRTI⁺ patients, but not ART-naïve patients, had significantly decreased mtDNA content, more frequent mtDNA deletions and COX-negative fibres than HIV^­ controls. However, in peripheral blood even HIV⁺ ART-naïve patients had depleted mtDNA. Decreased mtDNA in PBMC may therefore not be a relevant marker for NRTI-related mitochondrial toxicity.