Lipid oxidative markers are significantly increased in lipoatrophy but not in sustained asymptomatic hyperlactatemia.
The exact mechanism of lipoatrophy remains unclear. One hypothesized mechanism is accumulation of reactive oxygen free radicals, which is possibly related to dysfunctional mitochondria. We evaluated plasma levels of F2-isoprostanes-the most accurate method to measure oxidant stress in vivo-in a group of 59 nucleoside reverse transcriptase inhibitor-treated HIV-1-infected subjects. All had serial measurements of venous lactate levels as well as clinical evaluations for assessment of lipoatrophy and symptoms of mitochondrial toxicity. Overall, 16 subjects had sustained hyperlactatemia (4 of whom were symptomatic) and 43 had serial normal lactate levels. We found a significant increase in circulating products of lipid peroxidation, F2-isoprostanes (nanograms per milliliter), in subjects with lipoatrophy when compared with subjects without lipoatrophy (0.060 +/- 0.025 vs. 0.0420 +/- 0.02, respectively; P = 0.02). Interestingly, there was no significant difference in F2-isoprostane levels (nanograms per milliliter) between patients with persistently normal lactate and those who exhibited a sustained asymptomatic hyperlactatemia (0.053 +/- 0.027 vs. 0.053 +/- 0.021, respectively; P > 0.05). This could be explained by the yet unclear significance of asymptomatic hyperlactatemia, even in a setting like ours, where lactate levels were measured with close attention to the method of collection and processing. In contrast, the 4 subjects with symptomatic hyperlactatemia/lactic acidosis had a significant increase in their F2-isoprostanes compared with subjects with asymptomatic sustained hyperlactatemia (0.082 +/- 0.021 vs. 0.053 +/- 0.021, respectively; P < 0.05).
D000140:Acidosis, Lactic / Q000209:etiology / Q000378:metabolism*; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D015415:Biomarkers; D004359:Drug Therapy, Combination; D028441:F2-Isoprostanes / Q000097:blood*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D015227:Lipid Peroxidation; D008060:Lipodystrophy / Q000209:etiology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*
D019380:Anti-HIV Agents; D015415:Biomarkers; D028441:F2-Isoprostanes; D018894:Reverse Transcriptase Inhibitors