title: Muscle and liver lactate metabolism in HAART-treated and naive HIV-infected patients: the MITOVIR study.
abstract: 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.
authors.affiliation: Department des Maladies Infectieuses, CHU Pitié-Salpétrière, AP-HP, Université Pierre et Marie Curie, Paris, France. jade.ghosn@psl.ap-hop-paris.fr
authors.forename: Jade
authors.initials: J
authors.lastname: Ghosn
authors.forename: Marguerite
authors.initials: M
authors.lastname: Guiguet
authors.forename: Claude
authors.initials: C
authors.lastname: Jardel
authors.forename: Rabah
authors.initials: R
authors.lastname: Benyaou
authors.forename: Valérie
authors.initials: V
authors.lastname: Zeller
authors.forename: Anne
authors.initials: A
authors.lastname: Simon
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Valantin
authors.forename: Bahia
authors.initials: B
authors.lastname: Amellal
authors.forename: Lambert
authors.initials: L
authors.lastname: Assoumo
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Hogrel
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.forename: Anne
authors.initials: A
authors.lastname: Lombès
mesh_terms: D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism
chemical_list: D019344:Lactic Acid