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-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 C-methionine, CO2 exhalation was determined by infrared spectroscopy. MtDNA content in PBMCs was assessed by real-time polymerase chain reaction quantification.


RESULTS
CO2 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.
Banasch
Matthias
M
Department of Internal Medicine, St. Josef-Hospital, University of Bochum, Bochum, Germany. mbanasch@gmx.de
Goetze
Oliver
O
Hollborn
Ivo
I
Hochdorfer
Bettina
B
Bulut
Kerem
K
Schlottmann
Renate
R
Hagemann
Dirk
D
Brockmeyer
Norbert H
NH
Schmidt
Wolfgang E
WE
Schmitz
Frank
F
D000328:Adult; D001944:Breath Tests; D002247:Carbon Isotopes; D003430:Cross-Sectional Studies; D004272:DNA, Mitochondrial / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D019344:Lactic Acid / Q000097:blood*; D008297:Male; D008715:Methionine / Q000032:analysis*; D008930:Mitochondria, Liver / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012044:Regression Analysis
D002247:Carbon Isotopes; D004272:DNA, Mitochondrial; D019344:Lactic Acid; D008715:Methionine