Insulin Sensitivity in Multiple Pathways Is Differently Affected During Zidovudine/Lamivudine-Containing Compared With NRTI-Sparing Combination Antiretroviral Therapy

M.G.A. van Vonderen, R.M.E. Blumer, E.A.M. Hassink, J. Sutinen, M.T. Ackermans, M.A. van Agtmael, H. Yki-Jarvinen, S.A. Danner, M.J. Serlie, H.P. Sauerwein, P. Reiss

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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.
Original languageEnglish
Pages (from-to)186-193
Number of pages8
JournalJaids-journal of Acquired Immune Deficiency Syndromes
Volume53
Issue number2
DOIs
Publication statusPublished - 1 Feb 2010

Keywords

  • antiretroviral therapy
  • glucose metabolism
  • HIV
  • HIV-associated lipodystrophy
  • HIV PROTEASE INHIBITORS
  • WOMENS INTERAGENCY HIV
  • GLUCOSE DISPOSAL
  • IN-VITRO
  • FAT REDISTRIBUTION
  • DIABETES-MELLITUS
  • INFECTED PATIENTS
  • HEALTHY-ADULTS
  • NEGATIVE MEN
  • RESISTANCE

Cite this

van Vonderen, M. G. A., Blumer, R. M. E., Hassink, E. A. M., Sutinen, J., Ackermans, M. T., van Agtmael, M. A., Yki-Jarvinen, H., Danner, S. A., Serlie, M. J., Sauerwein, H. P., & Reiss, P. (2010). Insulin Sensitivity in Multiple Pathways Is Differently Affected During Zidovudine/Lamivudine-Containing Compared With NRTI-Sparing Combination Antiretroviral Therapy. Jaids-journal of Acquired Immune Deficiency Syndromes, 53(2), 186-193. https://doi.org/10.1097/QAI.0b013e3181c190f4