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


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.
Milazzo
Laura
L
Institute of Infectious and Tropical Diseases, University of Milan, L. Sacco Hospital, Via GB Grassi 74, 20157 Milan, Italy. laura.milazzo@virgilio.it
Piazza
Manuela
M
Sangaletti
Ornella
O
Gatti
Nadia
N
Cappelletti
Anna
A
Adorni
Fulvio
F
Antinori
Spinello
S
Galli
Massimo
M
Moroni
Mauro
M
Riva
Agostino
A
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D001944:Breath Tests / Q000379:methods*; D002245:Carbon Dioxide / Q000378:metabolism; D002247:Carbon Isotopes / Q000008:administration & dosage; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008715:Methionine / Q000008:administration & dosage; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000187:drug effects*; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*
D019380:Anti-HIV Agents; D002247:Carbon Isotopes; D018894:Reverse Transcriptase Inhibitors; D002245:Carbon Dioxide; D008715:Methionine