One year after AZD2281 d-drug switching, 13C-exhalation had recovered and almost reached normal values (6.09±2.5 vs. 6.30±1.4 in pooled HIV-negative controls; difference not

significant). Our results also support the hypothesis that mitochondrial function, at least in hepatic cells, is a dynamic process with a high regenerative capacity, particularly in the absence of other hepatotoxic factors. This is illustrated in two patients in our study who had acute HCV coinfection and who experienced a sharp decline in 13C-exhalation from baseline values that was completely reversible after HCV elimination. It is noteworthy that individuals receiving ART regimens without d-drugs (d4T or ddI) did not show any differences at the second MeBT measurement compared with baseline, irrespective of whether they switched the PI or NNRTI component or remained on stable baseline treatment. Overall, the breath test performance in this group was also indistinguishable from that of pooled HIV-negative controls, suggesting that modern (thymidine-analogue- and/or d-drug-sparing) ART per se has no negative impact on hepatic mitochondrial integrity, at least over 12 months. Moreover, the results of our study indicate that uncontrolled

selleck inhibitor viral replication might affect hepatic mitochondrial function in a much more deleterious way than ART does. Although the small size of the STI subgroup does not allow a definitive conclusion to be drawn, it is clear from this study

that 13C-exhalation decreased in all subgroups without ART at follow-up measurement. The 13C-methionine breath test is still lacking validation with an accepted Dapagliflozin ‘gold’ standard diagnostic test of (hepatic) mitochondrial function. What is more, we are not certain that such a standard exists. Histological data from other patient groups with ‘mitochondrial’ liver diseases (nonalcoholic steatohepatitis and chronic hepatitis C infection) indicate a good correlation of individual breath test outcome with histomorphological characteristics (degree of steatosis, inflammation grade, etc.) in nonalcoholic steatohepatitis but not in chronic HCV infection [18,19]. In the latter cohort, baseline HCV viral load was the only parameter with a tendency to correlate with MeBT results. This finding may also support the ‘oxidative stress hypothesis’ of uncontrolled viral replication, which may also account for possible HIV-associated mitochondrial damage in the present study. Before recommending the MeBT as a standard diagnostic of hepatic mitochondrial function it would be necessary to further explore these subcellular changes using more suitable techniques providing insights into hepatic mitochondrial morphology and function by measuring variables such as oxygen consumption and mitochondrial DNA content directly in liver tissue.