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JAC Advance Access published online on December 8, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh497
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JAC © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved
Received July 19, 2004
Revised October 4, 2004
Accepted October 6, 2004

Original article

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

Laura Milazzo 1*, Manuela Piazza 1, Ornella Sangaletti 2, Nadia Gatti 1, Anna Cappelletti 1, Fulvio Adorni 3, Spinello Antinori 1, Massimo Galli 1, Mauro Moroni 1, and Agostino Riva 1

1 Institute of Infectious and Tropical Diseases, University of Milan, L. Sacco Hospital, Via GB Grassi 74, 20157 Milan, Italy
2 Gastroenterology Unit, L. Sacco Hospital, Milan, Italy
3 Institute of Biomedical Technologies-National Research Council, Milan, Italy

* To whom correspondence should be addressed.
Laura Milazzo, E-mail: laura.milazzo{at}virgilio.it


  Abstract

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 {delta} 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.
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