Plasma mitochondrial DNA levels are inversely associated with HIV-RNA levels and directly with CD4 counts: potential role as a biomarker of HIV replication

Objectives: To evaluate plasma mitochondrial DNA (mtDNA) levels among HIV-infected patients and its potential role as a biomarker of residual viral replication. Methods: HIV-infected patients on follow-up at a reference hospital in north-west Spain were selected. DNA was isolated from plasma samples and mtDNA levels were assessed using a quantitative real-time PCR assay. HIV-RNA levels and CD4+ cell counts were evaluated in the same blood samples used for plasma mtDNA quantification. Epidemiological and clinical variables were included for the analysis. Results: A total of 235 HIV-infected patients were included. Mean plasma mtDNA levels were 217 +/- 656 copies/mu L for naive (31.9%) and 364 +/- 939 copies/mu L for HIV-infected patients receiving ART and with suppressed viraemia (P = 0.043). Among the latter, mean plasma mtDNA levels were 149 +/- 440 copies/mu L for those with low-level viraemia (LLV; HIV-RNA 20-200 copies/mL), 265 +/- 723 copies/mu L for those with detected-not-quantified (DNQ) viraemia (HIV-RNA <20 copies/mL) and 644 +/- 1310 copies/mu L for those with not-detected (ND) viraemia. Of note, a linear trend (P = 0.006) was observed among virologically suppressed (LLV, DNQ and ND) patients. ND patients had higher mtDNA levels compared with LLV patients (P = 0.057). Moreover, mtDNA levels were inversely associated with HIV-RNA levels (Spearman's rho -0.191, P = 0.003) and directly associated with CD4+ counts (Spearman's rho 0.131, P = 0.046). Conclusions: Increased plasma mtDNA levels are associated with lower HIV-RNA levels and higher CD4+ cell counts. Among ART-suppressed patients, mtDNA levels were significantly higher in those with complete virological suppression (ND) than in those with LLV. These data suggest that plasma mtDNA levels might serve as a biomarker of residual HIV replication.