[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 5 10),
HIV-infected patients on antiretroviral therapy with (n 5 6) and without (n 5 15) hyperlactataemia and
naive HIV-infected patients (n 5 11). After oral administration of [13C]methionine (2 mg/kg body weight),
hepatic methionine metabolism was measured by breath 13CO2 enrichment, expressed as d 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 5 0.001). HIVinfected
patients on antiretroviral therapy with normal serum lactate had reduced exhalation of 13CO2
compared with healthy subjects (DOB mean peak: 8.82 6 0.62 versus 11 6 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 6 0.68 versus 8.82 6 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.