An open-label, randomized study of the impact on insulin sensitivity, lipid profile and vascular inflammation by treatment with lopinavir/ritonavir or raltegravir in HIV-negative male volunteers

Antivir Ther. 2017;22(2):145-151. doi: 10.3851/IMP3098. Epub 2016 Oct 6.


Background: We aimed to measure the effect of raltegravir (RAL) on insulin sensitivity and surrogates of cardiovascular risk in healthy HIV-seronegative volunteers compared to that of lopinavir/r (LPV/r), a positive control.

Methods: An open-label, two phase crossover study in HIV-negative male subjects randomized 1:1 to receive either 2 weeks of LPV/r followed by a 2-week washout period and 2 weeks of RAL, or RAL initially followed by LPV/r. A hyperinsulinaemic euglycaemic clamp was performed prior to and following each 2-week dosing phase. Fasting samples for lipids, adiponectin, leptin, vascular inflammatory biomarkers and CD36 were also taken.

Results: A total of 16 subjects completed the study. At the baseline visit the mean insulin-stimulated glucose disposal per unit insulin (M/I) was 7.97 and 8.30 for LPV/r and RAL, respectively. The mean (sem) percentage change from baseline was -16.10% (3.84) after 2 weeks of LPV/r and -0.43% (4.83) after 2 weeks of RAL. Absolute M/I was 25% lower for LPV/r than for RAL (P=0.001). Triglycerides and total cholesterol rose significantly with LPV/r (+0.5 mmol/l, P=0.002 and +0.4 mmol/l, P<0.0001), but were unchanged with RAL. Proathrogenic lipid subfractions of low-density lipoprotein (LDL) cholesterol increased with LPV/r and were unaffected with RAL. LDL peak and mean particle diameter and LDL I significantly decreased with LPV/r (P<0.05), and trend of increased LDL III was detected. High-sensitivity C-reactive protein declined with RAL (-0.2 mg/l, P=0.043) but was elevated after LPV/r (+0.25 mg/l, P=0.03).

Conclusions: RAL was not associated with measurable change in glycaemic, metabolic or inflammatory effects.

Publication types

  • Clinical Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / blood
  • Adolescent
  • Adult
  • Anti-HIV Agents / administration & dosage*
  • C-Reactive Protein / metabolism
  • CD36 Antigens / blood
  • Cholesterol / blood
  • Cholesterol, LDL / blood
  • Cross-Over Studies
  • Glucose Clamp Technique
  • Healthy Volunteers
  • Humans
  • Insulin Resistance
  • Leptin / blood
  • Lopinavir / administration & dosage*
  • Male
  • Middle Aged
  • Raltegravir Potassium / administration & dosage*
  • Random Allocation
  • Ritonavir / administration & dosage*
  • Triglycerides / blood


  • ADIPOQ protein, human
  • Adiponectin
  • Anti-HIV Agents
  • CD36 Antigens
  • Cholesterol, LDL
  • Leptin
  • Triglycerides
  • Lopinavir
  • Raltegravir Potassium
  • C-Reactive Protein
  • Cholesterol
  • Ritonavir