Muscle and liver lactate metabolism in HAART-treated and naive HIV-infected patients: the MITOVIR study.

Objective: To assess the impact of nucleoside analogue reverse transcriptase inhibitor (NRTI) combination therapy on muscle and liver lactate metabolism in HIV-infected patients. Methods: This cross-sectional study involved HIV-infected patients who were either antiretroviral-naive (Group 1) or were receiving either a stable triple-drug combination including at least one d-drug (zidovudine, zalcitabine, stavudine, didanosine; Group 2) or a backbone of abacavir and lamivudine (Group 3). Lactataemia was measured at rest. Muscle lactate metabolism was assessed during a standardized exercise test and liver lactate metabolism during intravenous lactate infusion. Mitochondrial DNA was quantified in peripheral blood mononuclear cells. Results: A total of 65 patients were enrolled (16, 31 and 18 patients in Group 1, Group 2 and Group 3, respectively). None of the patients had symptoms of hyperlactataemia. Patients in Group 3 had received d-drugs for a median of seven years before switching to abacavir and lamivudine. Median baseline lactataemia, although within the normal range, was significantly higher in both treatment groups than in the naive patients (Group 2: 1.4, Group 3: 1.5, and Group 1: 1.0 mmol/l, P=0.005). Muscle lactate clearance was significantly lower in both treatment groups than in naive patients (Group 2: 1.6, Group 3: 1.8, and Group 1: 2.1, P=0.01). Lactate liver metabolism and mitochondrial DNA levels did not differ among the three groups. Conclusions: In HIV-infected patients without symptomatic hyperlactataemia, all NRTI-containing HAART regimens appear to cause muscle mitochondrial damage but to spare the liver. Absence of difference between Group 2 and Group 3 raises questions about the potential reversibility of muscle mitochondrial dysfunction, and/or the ability of abacavir and lamivudine to induce such mitochondrial damage.