[13C]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 [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