title: Changes in fat mitochondrial DNA and function in subjects randomized to abacavir-lamivudine or tenofovir DF-emtricitabine with atazanavir-ritonavir or efavirenz: AIDS Clinical Trials Group study A5224s, substudy of A5202.
abstract: BACKGROUND
  The effect of nonthymidine nucleoside reverse-transcriptase inhibitors (NRTIs) on fat mitochondrial DNA (mtDNA) content and function is unclear.
  
  
  METHODS
  A5202 randomized antiretroviral therapy-naive human immunodeficiency virus-infected subjects to abacavir-lamivudine (ABC/3TC) versus tenofovir DF-emtricitabine (TDF/FTC) with efavirenz (EFV) or atazanavir-ritonavir (ATV/r). A5224s, substudy of A5202, enrolled 269 subjects with fat measurements by dual-energy x-ray absorptiometry and computed tomography. A subset of subjects underwent fat biopsies at baseline and week 96 for mtDNA content (real-time polymerase chain reaction) and oxidative phosphorylation nicotinamide adenine dinucleotide (reduced) dehydrogenase (complex I) and cytochrome c oxidase (complex IV) activity levels (immunoassays). Intent-to-treat analyses were performed using analysis of variance and paired t tests.
  
  
  RESULTS
  Fifty-six subjects (87% male; median age, 39 years) were included; their median body mass index, CD4 cell count, and fat mtDNA level were 26 kg/m(2), 227 cells/μL, and 1197 copies/cell, respectively. Fat mtDNA content decreased within the ABC/3TC and TDF/FTC groups (combining EFV and ATV/r arms; median change, -341 [interquartile range, -848 to 190; P = .03] and -400 [-661 to -221; P < .001] copies/cell, respectively), but these changes did not differ significantly between the 2 groups (P = .57). Complex I and IV activity decreased significantly in the TDF/FTC group (median change, -12.45 [interquartile range, -24.70 to 2.90; P = .003] and -8.25 [-13.90 to -1.30; P < .001], optical density × 10(3)/µg, respectively) but not the ABC/3TC group. Differences between the ABC/3TC and TDF/FTC groups were significant for complex I (P = .03).
  
  
  CONCLUSIONS
  ABC/3TC and TDF/FTC significantly and similarly decreased fat mtDNA content, but only TDF/FTC decreased complex I and complex IV activity levels.
  
  
  BACKGROUND
  NCT00118898.
authors.affiliation: Case Western Reserve University, Cleveland, Ohio 44106, USA. grace.mccomsey@case.edu
authors.forename: Grace A
authors.initials: GA
authors.lastname: McComsey
authors.forename: Eric S
authors.initials: ES
authors.lastname: Daar
authors.forename: MaryAnn
authors.initials: M
authors.lastname: O'Riordan
authors.forename: Ann C
authors.initials: AC
authors.lastname: Collier
authors.forename: Lisa
authors.initials: L
authors.lastname: Kosmiski
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Santana
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Fichtenbaum
authors.forename: Heidi
authors.initials: H
authors.lastname: Fink
authors.forename: Paul E
authors.initials: PE
authors.lastname: Sax
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Libutti
authors.forename: Mariana
authors.initials: M
authors.lastname: Gerschenson
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000069446:Atazanavir Sulfate; D048588:Benzoxazines / Q000008:administration & dosage / Q000627:therapeutic use; D003521:Cyclopropanes; D004272:DNA, Mitochondrial / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000627:therapeutic use; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D039682:HIV-Associated Lipodystrophy Syndrome / Q000503:physiopathology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008928:Mitochondria / Q000187:drug effects; D009842:Oligopeptides / Q000008:administration & dosage / Q000627:therapeutic use; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use; D000068698:Tenofovir; D016896:Treatment Outcome; D000099227:Abacavir
chemical_list: D000225:Adenine; D000480:Alkynes; D019380:Anti-HIV Agents; D000069446:Atazanavir Sulfate; D048588:Benzoxazines; D003521:Cyclopropanes; D004272:DNA, Mitochondrial; D003841:Deoxycytidine; D015224:Dideoxynucleosides; D004338:Drug Combinations; D000068679:Emtricitabine; D019259:Lamivudine; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D019438:Ritonavir; D000068698:Tenofovir; C492871:abacavir, lamivudine drug combination; D000099227:Abacavir; C098320:efavirenz