title: Mitochondrial abnormalities in HIV-infected lipoatrophic patients treated with antiretroviral agents.
abstract: BACKGROUND
  Lipodystrophy is now widely described in HIV infected patients under antiretroviral regimen with important psychological impact. But physiopathology of loss of fat mass is still debated and the role of mitochondrial impairment is not clearly defined.
  
  
  OBJECTIVE
  To correlate clinical lipoatrophy (LA) in HIV patients with long-term treatment by nucleoside reverse transcriptase inhibitors (NRTIs) and muscular impairment related to mitochondrial dysfunction.
  
  
  METHODS
  Ten consecutive patients with clinical LA and 10 nonlipodystrophic (NLD) individuals on antiretroviral therapy were included. Patients underwent the following investigations: dual-energy x-ray absorptiometry (DEXA) scanning and lactate kinetics during standardized exercise. The mitochondrial respiratory complex activity (III and IV) and histoenzymatic abnormalities (classified as none, mild, or severe) were evaluated on muscle tissue obtained by biopsy in deltoid muscle.
  
  
  RESULTS
  Mean NRTI exposure was longer in the LA group than in the NLD group (81 +/- 30 months vs. 59 +/- 15 months), but mean protease inhibitor exposure was identical in both groups. Mean fat mass distribution for leg in the LA and NLD groups was 860 +/- 381 g versus 1895 +/- 999 g, respectively. The lactic acidosis threshold during exercise was reached in the LA group at lower workloads (mean: 45 +/- 17 W in the LA group vs. 68 +/- 11 W in the NLD group), and maximum power output exercise was restricted in LA patients (mean: 115 +/- 30 W vs. 153 +/- 28 W). Total complex activities in muscular tissue were lower in LA patients: the median (range) for complex III was 67 (1-128) versus 112 (28-143), and the median (range) for complex IV was 28 (1-70) versus 42 (1-75). Six patients had severe histoenzymatic abnormalities in the LA group versus none in the NLD group.
  
  
  CONCLUSIONS
  Clinical LA, confirmed by DEXA, in long-term NRTI-treated patients was associated with muscular mitochondrial dysfunction as shown by rapid lactic acidemia increase, impairment of respiratory chain activity for complexes III and IV, and mitochondrial histoenzymatic abnormalities.
authors.affiliation: Infectious Diseases Department, Rennes University Hospital, Rennes, France. jean-marc.chapplain@chu-rennes.fr
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Chapplain
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Beillot
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Begue
authors.forename: Faouzi
authors.initials: F
authors.lastname: Souala
authors.forename: Cécile
authors.initials: C
authors.lastname: Bouvier
authors.forename: Cédric
authors.initials: C
authors.lastname: Arvieux
authors.forename: Pierre
authors.initials: P
authors.lastname: Tattevin
authors.forename: Mathieu
authors.initials: M
authors.lastname: Dupont
authors.forename: Françoise
authors.initials: F
authors.lastname: Chapon
authors.forename: Régis
authors.initials: R
authors.lastname: Duvauferrier
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hespel
authors.forename: Pierre
authors.initials: P
authors.lastname: Rochcongar
authors.forename: Christian
authors.initials: C
authors.lastname: Michelet
mesh_terms: D015502:Absorptiometry, Photon; D000140:Acidosis, Lactic / Q000097:blood / Q000139:chemically induced*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008060:Lipodystrophy / Q000139:chemically induced*; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000187:drug effects; D028361:Mitochondrial Diseases / Q000150:complications*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D044966:Anti-Retroviral Agents; D018894:Reverse Transcriptase Inhibitors