Related Experiment Video
Updated: Jun 18, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Insulin sensitivity in multiple pathways is differently affected during zidovudine/lamivudine-containing compared
Marit G A van Vonderen1, Regje M E Blümer, Elly A M Hassink
1Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands. m.van.vonderen@znb.nl
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.
Related Concept Videos
Retrovirus Life Cycles
Antiviral Nucleoside Inhibitors
Oral Hypoglycemic Agents: Biguanides and Glitazones
Pharmacokinetics in Pediatric Patients: Drug Excretion
Insulin: Dosing Regimen and Adverse Effects
The basal dose constitutes about 40%-50% of the total daily dose, with the rest as premeal insulin. The mealtime insulin dose should mirror...
Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment

