Insulin sensitivity in multiple pathways is differently affected during zidovudine/lamivudine-containing compared with NRTI-sparing combination antiretroviral therapy.
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.
van Vonderen
Marit G A
MG
Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands. m.van.vonderen@znb.nl
Blümer
Regje M E
RM
Hassink
Elly A M
EA
Sutinen
Jussi
J
Ackermans
Mariette T
MT
van Agtmael
Michiel A
MA
Yki-Jarvinen
Hannele
H
Danner
Sven A
SA
Serlie
Mireille J
MJ
Sauerwein
Hans P
HP
Reiss
Peter
P
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*
D019380:Anti-HIV Agents; D001786:Blood Glucose; D008055:Lipids; D019259:Lamivudine; D015215:Zidovudine