title: 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.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  RAL was not associated with measurable change in glycaemic, metabolic or inflammatory effects.
authors.affiliation: St Stephen's AIDS Trust, Chelsea and Westminster Hospital, London, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Randell
authors.affiliation: St Stephen's AIDS Trust, Chelsea and Westminster Hospital, London, UK.|Present: Institute of Translational Medicine, University of Liverpool, Liverpool, UK.|Present: Gilead Sciences Ltd., London, UK.
authors.forename: Akil
authors.initials: A
authors.lastname: Jackson
authors.affiliation: St Stephen's AIDS Trust, Chelsea and Westminster Hospital, London, UK.|Present: Research Department of Infection and Population Health, University College London, London, UK.
authors.forename: Ana
authors.initials: A
authors.lastname: Milinkovic
authors.affiliation: St Stephen's AIDS Trust, Chelsea and Westminster Hospital, London, UK.
authors.forename: Marta
authors.initials: M
authors.lastname: Boffito
authors.affiliation: St Stephen's AIDS Trust, Chelsea and Westminster Hospital, London, UK.
authors.forename: Graeme
authors.initials: G
authors.lastname: Moyle
mesh_terms: D052242:Adiponectin / Q000097:blood; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D002097:C-Reactive Protein / Q000378:metabolism; D018955:CD36 Antigens / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D015309:Glucose Clamp Technique; D064368:Healthy Volunteers; D006801:Humans; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D061466:Lopinavir / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D000068898:Raltegravir Potassium / Q000008:administration & dosage*; D011897:Random Allocation; D019438:Ritonavir / Q000008:administration & dosage*; D014280:Triglycerides / Q000097:blood
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D019380:Anti-HIV Agents; D018955:CD36 Antigens; D008078:Cholesterol, LDL; D020738:Leptin; D014280:Triglycerides; D061466:Lopinavir; D000068898:Raltegravir Potassium; D002097:C-Reactive Protein; D002784:Cholesterol; D019438:Ritonavir