title: HIV-1 infection and first line ART induced differential responses in mitochondria from blood lymphocytes and monocytes: the ANRS EP45 "Aging" study.
abstract: BACKGROUND
  The ANRS EP45 "Aging" study investigates the cellular mechanisms involved in the accelerated aging of HIV-1 infected and treated patients. The data reported focus on mitochondria, organelles known to be involved in cell senescence.
  
  
  METHODS
  49 HIV-1 infected patients untreated with antiretroviral therapy, together with 49 seronegative age- and sex-matched control subjects and 81 HIV-1 infected and treated patients, were recruited by 3 AIDS centres (Marseille, Montpellier, Nice; France; http://clinicaltrials.gov/, NCT01038999). In more than 88% of treated patients, the viral load was <40 copies/ml and the CD4+ cell count was >500/mm(3). ROS (reactive oxygen species) production and ΔΨm (inner membrane potential) were measured by flow cytometry in blood lymphocytes and monocytes (functional parameters). Three mitochondrial network quantitative morphological parameters were computed using confocal microscopy and image analysis. Three PBMC mitochondrial proteins (porin and subunits 2 and 4 of cytochrome C oxidase encoded by mtDNA or nuclear DNA, respectively) were analysed by western blotting.
  
  
  RESULTS
  Quantitative changes in PBMC mitochondrial proteins were not induced by either HIV-1 infection or ART. Discriminant analysis integrating functional (ROS production and ΔΨm) or morphological (network volume density, fragmentation and branching) parameters revealed HIV-1 infection and ART differential effects according to cell type. First line ART tended to rescue lymphocyte mitochondrial parameters altered by viral infection, but induced slight changes in monocytes. No statistical difference was found between the effects of three ART regimens on mitochondrial parameters. Correlations between functional parameters and viral load confirmed the damaging effects of HIV-1 in lymphocyte mitochondria.
  
  
  CONCLUSIONS
  In patients considered to be clinically stable, mitochondria exhibited functional and morphological modifications in PBMCs resulting from either direct or indirect effects of HIV-1 infection (lymphocytes), or from first line ART (monocytes). Together with other tissue impairments, these changes may contribute to global aging.
authors: Inserm UMR 910, Aix-Marseille Univ, Marseille, France.
authors: Sophie
authors: S
authors: Perrin
authors: Jonathan
authors: J
authors: Cremer
authors: Patrice
authors: P
authors: Roll
authors: Olivia
authors: O
authors: Faucher
authors: Amélie
authors: A
authors: Ménard
authors: Jacques
authors: J
authors: Reynes
authors: Pierre
authors: P
authors: Dellamonica
authors: Alissa
authors: A
authors: Naqvi
authors: Joëlle
authors: J
authors: Micallef
authors: Elisabeth
authors: E
authors: Jouve
authors: Catherine
authors: C
authors: Tamalet
authors: Caroline
authors: C
authors: Solas
authors: Christel
authors: C
authors: Pissier
authors: Isabelle
authors: I
authors: Arnoux
authors: Corine
authors: C
authors: Nicolino-Brunet
authors: Léon
authors: L
authors: Espinosa
authors: Nicolas
authors: N
authors: Lévy
authors: Elise
authors: E
authors: Kaspi
authors: Andrée
authors: A
authors: Robaglia-Schlupp
authors: Isabelle
authors: I
authors: Poizot-Martin
authors: Pierre
authors: P
authors: Cau
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D005260:Female; D015658:HIV Infections / Q000503:physiopathology*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*
chemical_list: D019380:Anti-HIV Agents