Journal Article

[<sup>13</sup>C]Methionine breath test: a novel method to detect antiretroviral drug-related mitochondrial toxicity

Laura Milazzo, Manuela Piazza, Ornella Sangaletti, Nadia Gatti, Anna Cappelletti, Fulvio Adorni, Spinello Antinori, Massimo Galli, Mauro Moroni and Agostino Riva

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 55, issue 1, pages 84-89
Published in print January 2005 | ISSN: 0305-7453
Published online January 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dkh497
[13C]Methionine breath test: a novel method to detect antiretroviral drug-related mitochondrial toxicity

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Objectives: A major side effect of antiretroviral drugs is nucleoside reverse transcriptase inhibitor (NRTI)-related mitochondrial toxicity, the in vivo diagnosis of which is difficult and not yet standardized. We used the [13C]methionine breath test to investigate hepatic mitochondrial oxidation in HIV-1-infected patients receiving antiretroviral therapy.

Patients and methods: The [13C]methionine breath test was performed in healthy subjects (n=10), HIV-infected patients on antiretroviral therapy with (n=6) and without (n=15) hyperlactataemia and naive HIV-infected patients (n=11). After oral administration of [13C]methionine (2 mg/kg body weight), hepatic methionine metabolism was measured by breath 13CO2 enrichment, expressed as δ over baseline (DOB) every 15 min for 120 min by mass spectrometry.

Results: The four study groups showed a significant difference in 13CO2 exhalation (P=0.001). HIV-infected patients on antiretroviral therapy with normal serum lactate had reduced exhalation of 13CO2 compared with healthy subjects (DOB mean peak: 8.82±0.62 versus 11±0.9, P<0.05). HIV patients with hyperlactataemia had even lower values when compared with patients with normal lactataemia (DOB mean peak: 4.98±0.68 versus 8.82±0.62, P<0.05).

Conclusions: The [13C]methionine breath test possibly showed mitochondrial impairment in antiretroviral-treated HIV-positive patients, particularly with hyperlactataemia. This non-invasive test can be used to monitor drug-related mitochondrial toxicity in vivo and to discover early and asymptomatic damage of the respiratory chain.

Keywords: lactic acidosis; liver toxicity; nucleoside reverse transcriptase inhibitors

Journal Article.  3710 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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