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 [(13)C]methionine breath test to investigate hepatic mitochondrial oxidation in HIV-1-infected patients receiving antiretroviral therapy. PATIENTS AND METHODS: The [(13)C]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 [(13)C]methionine (2 mg/kg body weight), hepatic methionine metabolism was measured by breath (13)CO(2) 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 (13)CO(2) exhalation (P=0.001). HIV-infected patients on antiretroviral therapy with normal serum lactate had reduced exhalation of (13)CO(2) 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 [(13)C]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.
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 [(13)C]methionine breath test to investigate hepatic mitochondrial oxidation in HIV-1-infectedpatients receiving antiretroviral therapy. PATIENTS AND METHODS: The [(13)C]methionine breath test was performed in healthy subjects (n=10), HIV-infectedpatients on antiretroviral therapy with (n=6) and without (n=15) hyperlactataemia and naive HIV-infectedpatients (n=11). After oral administration of [(13)C]methionine (2 mg/kg body weight), hepatic methionine metabolism was measured by breath (13)CO(2) 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 (13)CO(2) exhalation (P=0.001). HIV-infectedpatients on antiretroviral therapy with normal serum lactate had reduced exhalation of (13)CO(2) compared with healthy subjects (DOB mean peak: 8.82+/-0.62 versus 11+/-0.9, P<0.05). HIVpatients 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 [(13)C]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.
Authors: Sven H Stüwe; Oliver Goetze; Larissa Arning; Matthias Banasch; Wolfgang E Schmidt; Ludger Schöls; Carsten Saft Journal: BMC Neurol Date: 2011-11-15 Impact factor: 2.474
Authors: Fan Lam; James Chu; Ji Sun Choi; Chang Cao; T Kevin Hitchens; Scott K Silverman; Zhi-Pei Liang; Ryan N Dilger; Gene E Robinson; King C Li Journal: Proc Natl Acad Sci U S A Date: 2022-03-02 Impact factor: 12.779