13C-Methionine breath test detects distinct hepatic mitochondrial dysfunction in HIV-Infected patients with normal serum lactate

Objective: To assess mitochondrial respiratory chain dysfunction in different treatment groups of HIV-infected patients with normal serum lactate by measuring hepatic mitochondrial decarboxylation capacity by the C-13-methionine breath test (MeBT) and to correlate MeBT results with mitochondrial DNA (mtDNA) content in peripheral blood mononuclear cells (PBMCs). Methods: Four groups were studied: HIV-negative controls (n = 10), treatment-naive patients (n = 15), antiretroviral therapy (ART)treated patients with asymptomatic disease (n = 15), and patients with long-term treatment and clinical evidence of lipoatrophy (n = 15). After oral administration of 13 C-methionine, (CO2)-C-13 exhalation was determined by infrared spectroscopy. MtDNA content in PBMCs was assessed by real-time polymerase chain reaction quantification. Results: (CO2)-C-13 exhalation in lipoatrophic patients and therapy-naive patients was distinctly decreased when compared with that in healthy controls and asymptomatic patients (P < 0.001). The functional mitochondrial impairment in lipoatrophic patients was associated with a 47% decline in mtDNA content. MeBT results and mtDNA were significantly correlated in ART-treated patients (r = 0.77, P < 0.0001). Conclusions: MeBT is a simple noninvasive method to detect mitochondrial dysfunction in HIV-infected patients that correlates with mtDNA depletion in PBMCs of ART-treated individuals. Decreased hepatic methionine metabolism in therapy-naive patients may reflect the functional relevance of viral-mediated mitochondrial toxicity.