title: Mitochondrial damage in adipose tissue of untreated HIV-infected patients.
abstract: OBJECTIVE
  antiretrovirals, especially thymidine-analogue nucleoside reverse transcriptase inhibitors (tNRTIs), may cause the mitochondrial damage in adipose tissue that has been associated with lipodystrophy development. HIV itself may damage blood cell mitochondria. However, the viral capacity to induce adipose tissue mitochondrial lesion is still a matter of doubt. We aimed to assess whether untreated HIV infection was associated with adipose tissue mitochondrial abnormalities.
  
  
  METHODS
  : Single-site, cross-sectional, controlled observational and exploratory study without intervention.
  
  
  METHODS
  we included 24 uninfected controls and 18 HIV-infected patients with undetectable viral load and no clinical signs of lipodystrophy stratified as antiretroviral naive (n = 11) or at least 6-month antiviral-treated with a double NRTI combination, including lamivudine plus one tNRTI (n = 7). Subcutaneous adipose tissue was homogenated to determine mtDNA content by rtPCR and mitochondrial function per mitochondria through the spectrophotometric measurement of cytochrome c oxidase activity normalized by citrate synthase amount (COX/citrate synthase). Differences in mitochondrial parameters among groups were sought to determine the contribution of HIV and antiretrovirals to mitochondrial alterations.
  
  
  RESULTS
  compared with uninfected controls (arbitrarily assigned 100%), naive individuals presented a marked decrease in adipose tissue mtDNA content and COX/citrate synthase function (62 and 75% remaining content/activity, P < 0.001 and P < 0.05). Antiretrovirals did not increase this impairment (69 and 70% remaining content/activity, P < 0.05 compared to controls and P = not significant compared to naives). Additionally, molecular and functional mitochondrial parameters were positively correlated (P < 0.05).
  
  
  CONCLUSIONS
  in nonlipodystrophic HIV-infected naive patients, viral infection is associated with adipose tissue mtDNA decrease and mitochondrial dysfunction independently of antiretroviral treatment.
authors.affiliation: Mitochondrial Research Laboratory, Internal Medicine Department, Muscle Research Unit, IDIBAPS, University of Barcelona, Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Raras, Spain. garrabou@clinic.ub.es
authors.forename: Glòria
authors.initials: G
authors.lastname: Garrabou
authors.forename: Sònia
authors.initials: S
authors.lastname: López
authors.forename: Constanza
authors.initials: C
authors.lastname: Morén
authors.forename: Esteban
authors.initials: E
authors.lastname: Martínez
authors.forename: Joan
authors.initials: J
authors.lastname: Fontdevila
authors.forename: Francesc
authors.initials: F
authors.lastname: Cardellach
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Gatell
authors.forename: Oscar
authors.initials: O
authors.lastname: Miró
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D003430:Cross-Sectional Studies; D005260:Female; D015497:HIV-1; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects*; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*; D013030:Spain
chemical_list: D018894:Reverse Transcriptase Inhibitors