Abstract

Nucleoside reverse transcriptase inhibitors used in antiretroviral therapy may cause mitochondrial toxicity. Mitochondrial dysfunction leads to disturbance of the glucose metabolism, resulting in an accumulation of L-lactate. We tested the hypothesis that an oral glucose tolerance test (OGTT) can be used to detect mitochondrial toxicity in patients on antiretroviral nucleoside analogues. An OGTT was performed in 30 subjects: 16 HIV-infected treated patients without adverse events (group 1) and 14 HIV-infected patients with adverse events related to nucleoside reverse transcriptase inhibitor- induced mitochondrial toxicity (group 2). Lactate was measured at baseline and 60 and 120 min after glucose loading. At all time points the lactate levels were higher in the adverse events group compared to the other group, with the highest levels of lactate at t = 60 min (mean 1912 μmol/L, SD ± 609); mean lactates in the group without adverse events was 1429 μmol/L (SD ± 464). When levels above the upper limit of normal of 1800 μmol/L were used as an indication for mitochondrial toxicity, the sensitivity and specificity were 57% and 81%, respectively. The area under the ROC curve was 0.75. For L-lactate levels > 2000 μmol/L the specificity was 90%. An OGTT with measurement of lactate at baseline and one hour after glucose loading can detect (occult) hyperlactataemia in patients with mitochondrial impairment. From our study we suggest to perform an OGTT as an additional test in patients with symptoms suspect for adverse events to discern mitochondrial toxicity.

Keywords: HIV infection, mitochondrial toxicity, OGTT, lactate, nucleoside reverse transcriptase inhibitors, NRTI