Impact of antiretroviral treatment on (13) C-methionine metabolism as a marker of hepatic mitochondrial function: a longitudinal study.
OBJECTIVE
Uncontrolled viral replication and antiretroviral treatment (ART) may independently contribute to hepatic mitochondrial toxicity. The present study was designed to explore the longitudinal effects of treatment modifications on hepatic mitochondrial function by means of noninvasive (13) C-methionine breath test (MeBT) diagnostics.


METHODS
A total of 113 HIV-infected patients underwent two consecutive MeBTs over an interval of 11.8±3.5 months. Forty-nine patients remained on stable ART or no therapy; 28 participants switched ART; 27 patients (re)initiated ART, and nine individuals underwent a structured treatment interruption (STI) of ART between MeBTs 1 and 2. Breath test results were expressed as cumulative percentage dose of (13) CO(2) recovered after 1.5 h test time (cPDR(1.5h) ).


RESULTS
Initiation of ART in treatment-naïve individuals and patients on STI was associated with a significant improvement of hepatic mitochondrial function (P<0.05). Cessation of ART or a prolonged delay in initiating therapy in treatment-naïve patients in turn led to a significant decline of (13) C-exhalation compared with baseline (P<0.05). A marked increase in (13) C-exhalation was observed in individuals who switched from stavudine or ddI to tenofovir or abacavir (+170%; P<0.001), while no differences between MeBTs 1 and 2 were found in individuals on ART who had remained on stable regimens or in those who changed a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) component.


CONCLUSIONS
The present data suggest that hepatic mitochondrial function in HIV disease is a dynamic process with a high regenerative capacity and highlight the pathogenic relevance of HIV replication. Our findings suggest that modern ART per se does not negatively impact hepatic mitochondrial function.
Banasch
M
M
Department of Internal Medicine, St Josef-Hospital, Ruhr-University of Bochum, Bochum, Germany. mbanasch@gmx.de
Frank
J
J
Serova
K
K
Knyhala
K
K
Kollar
S
S
Potthoff
A
A
Brockmeyer
N H
NH
Goetze
O
O
D000208:Acute Disease; D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001944:Breath Tests; D002247:Carbon Isotopes; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000821:virology; D006801:Humans; D008107:Liver Diseases / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D008715:Methionine / Q000378:metabolism; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000821:virology; D011237:Predictive Value of Tests; D019562:Viral Load
D044966:Anti-Retroviral Agents; D002247:Carbon Isotopes; D008715:Methionine