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

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 [C-13]methionine breath test to investigate hepatic mitochondrial oxidation in HIV-1-infected patients receiving antiretroviral therapy. Patients and methods: The [C-13]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 [C-13]methionine (2 mg/kg body weight), hepatic methionine metabolism was measured by breath (CO2)-C-13 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 (CO2)-C-13 exhalation (P=0.001). HIV-infected patients on antiretroviral therapy with normal serum lactate had reduced exhalation of (CO2)-C-13 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 [C-13]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.