title: Zidovudine/lamivudine but not nevirapine in combination with lopinavir/ritonavir decreases subcutaneous adipose tissue mitochondrial DNA.
abstract: OBJECTIVE
  No randomized study has prospectively followed subcutaneous adipose tissue mitochondrial DNA (mtDNA) changes when starting thymidine nucleoside reverse transcriptase inhibitors (tNRTIs).
  
  
  METHODS
  The Metabolic Effects of DIfferent CLasses of AntiretroviralS study randomized HIV-positive, treatment-naive male participants to start lopinavir/ritonavir (LPVr) with either zidovudine/lamivudine (ZDV/3TC) or nevirapine (NVP).
  
  
  METHODS
  Regional body fat was assessed by dual energy x-ray absorptiometry and abdominal computed tomography at months 0, 3, 12, 24 and 36. In a molecular substudy, subcutaneous adipose tissue (SAT) biopsies were taken, with mtDNA quantified by quantitative PCR. Data were analyzed using repeated measures linear regression analyses.
  
  
  RESULTS
  Of 50 participants recruited (23 to LPVr/ZDV/3TC), 48 started therapy, and 37 participants (19 on LPVr/ZDV/3TC) enrolled in the substudy. At 36 months, the LPVr/ZDV/3TC group had significantly lower limb fat [6.4 kg (0.26) versus 7.3 kg (0.31), P = 0.017] and a trend toward lower abdominal SAT compared to the LPVr/NVP group [131 cm (6.86) versus 146 cm (6.33), P = 0.097]. Over 36 months, mtDNA declined in the LPVr/ZDV/3TC group [mtDNA region 1: -190 (95) copies/cell, P = 0.053, region 2: -269 (106) copies/cell, P = 0.016] but not within the LPVr/NVP group [region 1: +28 (99) copies/cell, P = 0.78, region 2: +51 (111) copies/cell, P = 0.65, between-group difference P < 0.01 for both measurements]. mtDNA was significantly lower in the LPVr/ZDV/3TC group at 36 months.
  
  
  CONCLUSIONS
  This is the first randomized study to prospectively demonstrate reductions in SAT mtDNA in patients initiating ZDV/3TC-containing antiretroviral therapy (ART) but not in those initiating nucleoside reverse transcriptase inhibitor-sparing ART containing NVP and protease inhibitor. That reductions in SAT mtDNA were also accompanied by lower limb fat suggests that use of ART not containing ZDV/3TC may help prevent development of peripheral lipoatrophy.
authors.affiliation: HIV Molecular Research Group, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland. eoinrua@gmail.com
authors.forename: Eoin R
authors.initials: ER
authors.lastname: Feeney
authors.forename: Marit G A
authors.initials: MG
authors.lastname: van Vonderen
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Wit
authors.forename: Sven A
authors.initials: SA
authors.lastname: Danner
authors.forename: Michiel A
authors.initials: MA
authors.lastname: van Agtmael
authors.forename: Francesc
authors.initials: F
authors.lastname: Villarroya
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Capeau
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.forename: Patrick W G
authors.initials: PW
authors.lastname: Mallon
mesh_terms: D015502:Absorptiometry, Photon; D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001284:Atrophy / Q000139:chemically induced / Q000517:prevention & control; D018791:CD4 Lymphocyte Count; D004272:DNA, Mitochondrial / Q000187:drug effects*; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D006679:HIV Seropositivity / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D015497:HIV-1 / Q000187:drug effects; D039682:HIV-Associated Lipodystrophy Syndrome / Q000097:blood / Q000473:pathology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000494:pharmacology*; D061466:Lopinavir / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000008:administration & dosage / Q000494:pharmacology*; D011446:Prospective Studies; D012367:RNA, Viral / Q000187:drug effects; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D019438:Ritonavir / Q000008:administration & dosage / Q000494:pharmacology*; D050151:Subcutaneous Fat / Q000187:drug effects* / Q000473:pathology*; D016896:Treatment Outcome; D055815:Young Adult; D015215:Zidovudine / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D004338:Drug Combinations; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; C109078:lamivudine, zidovudine drug combination; D061466:Lopinavir; D019259:Lamivudine; D015215:Zidovudine; D019829:Nevirapine; D019438:Ritonavir