title: Mitochondrial effects of antiretroviral therapies in asymptomatic patients.
abstract: BACKGROUND
  A decrease in the mitochondrial (mt) DNA to nuclear DNA ratio has gained acceptance as a marker of mitochondrial toxicity in treated HIV-infected patients, but the functional meaning of this alteration is unclear.
  
  
  METHODS
  We assessed mtDNA content, mitochondrial content and function in peripheral blood mononuclear cells (PBMCs) of consecutive asymptomatic HIV-infected patients. Patients selected had been receiving a first-line highly active antiretroviral therapy (HAART) regimen for at least 6 months, consisting of zidovudine plus lamivudine or stavudine plus didanosine plus either nelfinavir or nevirapine, or were antiretroviral-naive. The mtDNA content was assessed by quantitative real-time PCR, mitochondrial content by citrate synthase activity, enzyme activity of complexes III and IV (both partially encoded by mtDNA) of the electron transport chain by spectrophotometry, oxygen consumption by polarography, and oxidative damage in cell membranes by monitoring cis-parinaric acid fluorescence.
  
  
  RESULTS
  Mitochondrial content was significantly lower in all treated groups. Patients receiving stavudine plus didanosine had mtDNA depletion and a decrease in complex IV activity. However, oxygen consumption capacity and lipid peroxidation were unaffected in all groups.
  
  
  CONCLUSIONS
  Long-term HAART may induce mitochondrial abnormalities in PBMC mitochondria, which do not necessarily translate into functional abnormalities, at least in asymptomatic patients.
authors.affiliation: Muscle Research Unit, Department of Internal Medicine, Hospital Clinic, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), School of Medicine, University of Barcelona, Barcelona, Catalonia, Spain.
authors.forename: Sònia
authors.initials: S
authors.lastname: López
authors.forename: Oscar
authors.initials: O
authors.lastname: Miró
authors.forename: Esteban
authors.initials: E
authors.lastname: Martínez
authors.forename: Enric
authors.initials: E
authors.lastname: Pedrol
authors.forename: Benjamín
authors.initials: B
authors.lastname: Rodríguez-Santiago
authors.forename: Ana
authors.initials: A
authors.lastname: Milinkovic
authors.forename: Anna
authors.initials: A
authors.lastname: Soler
authors.forename: Miguel A
authors.initials: MA
authors.lastname: García-Viejo
authors.forename: Virginia
authors.initials: V
authors.lastname: Nunes
authors.forename: Jordi
authors.initials: J
authors.lastname: Casademont
authors.forename: Josep M
authors.initials: JM
authors.lastname: Gatell
authors.forename: Francesc
authors.initials: F
authors.lastname: Cardellach
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001483:Base Sequence; D003430:Cross-Sectional Studies; D017931:DNA Primers; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000235:genetics*; D016049:Didanosine / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D019888:Nelfinavir / Q000627:therapeutic use; D019829:Nevirapine / Q000627:therapeutic use; D016133:Polymerase Chain Reaction / Q000379:methods; D018119:Stavudine / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D017931:DNA Primers; D004272:DNA, Mitochondrial; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine; D019888:Nelfinavir; D016049:Didanosine