Identification and characterization of the molecular mechanisms contributing to the high incidence of insulin resistance in HIV infected patients treated with combined antiretroviral therapy remains a critically important goal in the quest to improve the safety of antiretroviral treatment regimens. The use of in vitro model systems together with the investigation of drug-mediated effects on glucose homeostasis in animals and healthy human volunteers has provided important insight into the contribution of individual drugs to insulin resistance and affected cellular pathways. HIV protease inhibitor mediated blockade of glucose transport and nucleoside reverse transcriptase inhibitor mediated mitochondrial toxicity have been well characterized. Together with growing understanding of mediators of insulin resistance in non-HIV metabolic syndrome, additional cellular effects including the induction of endoplasmic reticulum and oxidative stress, altered adipocytokine secretion, and lipotoxicity have been integrated into this developing picture. Further elucidation of these mechanisms provides potential for the continued development of safer antiviral drugs and targeted treatment of insulin resistance in affected patients.

Original languageEnglish
Pages (from-to)459-468
Number of pages10
JournalBest Practice and Research: Clinical Endocrinology and Metabolism
Issue number3
StatePublished - Jun 2011


  • ER stress
  • HIV protease inhibitors
  • adipocytokines
  • glucose transport
  • in vitro models
  • insulin sensitivity
  • lipotoxicity
  • nucleoside reverse transcriptase inhibitors


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