title: Insulin sensitivity in multiple pathways is differently affected during zidovudine/lamivudine-containing compared with NRTI-sparing combination antiretroviral therapy.
abstract: OBJECTIVE
  The extent and manner by which HIV nucleoside reverse transcriptase inhibitors contribute to insulin resistance is unclear. We evaluated the effect of zidovudine/lamivudine (ZDV/3TC) on glucose metabolism.
  
  
  METHODS
  combination antiretroviral therapy-naive men were randomized to lopinavir/ritonavir (LPV/r, 400/100 mg twice a day) + ZDV/3TC or LPV/r (533/133 mg twice a day) + nevirapine (NVP). Computerized tomography, dual-energy X-ray absorptiometry scans, and hyperinsulinemic euglycemic clamps using stable isotopes were performed before and after 3, 12, and 24 months of combination antiretroviral therapy.
  
  
  RESULTS
  Insulin-stimulated peripheral glucose disposal decreased by 25% after 3 months in patients on zidovudine/lamivudine/lopinavir/ritonavir (ZDV/3TC/LPV/r) (P < 0.001) and this decreased rate persisted thereafter, followed by a transient decrease in insulin-mediated inhibition of lipolysis. In the nevirapine/lopinavir/ritonavir (NVP/LPV/r) group, hepatic insulin sensitivity had improved compared with baseline after 24 months. After the initial 3 months, limb fat decreased in the ZDV/3TC/LPV/r arm up to 24 months [-849 +/- 345 g (P = 0.017)], and visceral adipose tissue increased over 2 years [+36.2 +/- 13.3 cm2 (P = 0.009)]. In the NVP/LPV/r group, a generalized increase in fat mass was observed.
  
  
  CONCLUSIONS
  Treatment with ZDV/3TC/LPV/r versus NVP/LPV/r differentially affects glucose and lipid metabolism. The ZDV/3TC/LPV/r regimen induced peripheral insulin resistance, a transient increase in basal lipolysis and a transient decrease in insulin-mediated inhibition of lipolysis, whereas hepatic insulin sensitivity improved with the NVP/LPV/r regimen.
authors.affiliation: Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands. m.van.vonderen@znb.nl
authors.forename: Marit G A
authors.initials: MG
authors.lastname: van Vonderen
authors.forename: Regje M E
authors.initials: RM
authors.lastname: Blümer
authors.forename: Elly A M
authors.initials: EA
authors.lastname: Hassink
authors.forename: Jussi
authors.initials: J
authors.lastname: Sutinen
authors.forename: Mariette T
authors.initials: MT
authors.lastname: Ackermans
authors.forename: Michiel A
authors.initials: MA
authors.lastname: van Agtmael
authors.forename: Hannele
authors.initials: H
authors.lastname: Yki-Jarvinen
authors.forename: Sven A
authors.initials: SA
authors.lastname: Danner
authors.forename: Mireille J
authors.initials: MJ
authors.lastname: Serlie
authors.forename: Hans P
authors.initials: HP
authors.lastname: Sauerwein
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects*; D001823:Body Composition / Q000187:drug effects; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000187:drug effects; D019259:Lamivudine / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008066:Lipolysis / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015215:Zidovudine / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D001786:Blood Glucose; D008055:Lipids; D019259:Lamivudine; D015215:Zidovudine