title: Effect of boosted fosamprenavir or lopinavir-based combinations on whole-body insulin sensitivity and lipids in treatment-naive HIV-type-1-positive men.
abstract: BACKGROUND
  Antiretroviral therapy is associated with metabolic complications, including dyslipidaemia, body fat changes and insulin resistance. Healthy volunteer studies have demonstrated a decrease in glucose disposal associated with dosing with specific antiretrovirals.
  
  
  METHODS
  HIV-type-1-positive male participants were randomized to receive tenofovir disoproxil fumarate and lamivudine, with either fosamprenavir (FPV)/ritonavir or lopinavir (LPV)/ritonavir twice daily. A hyperinsulinaemic euglycaemic clamp was performed at baseline and at 2 weeks after commencing treatment. The homeostasis model assessment index for insulin resistance (HOMA-IR) was also calculated at these time points. Changes in lipids and lipoprotein subfractions (by nuclear magnetic resonance spectroscopy) were assessed. A pharmacokinetic assessment was undertaken at week 2.
  
  
  RESULTS
  A total of 27 participants were enrolled. There was no significant change in whole-body insulin sensitivity or HOMA-IR from baseline or between groups. Total cholesterol increased significantly, by 6.6% with FPV and 10.9% with LPV. The changes in lipids and lipoprotein subfractions were similar between groups with increases in triglycerides, very low-density lipoprotein (VLDL) and chylomicrons, and low-density lipoprotein (LDL) particles. Although the total high-density lipoprotein (HDL) particles were not significantly altered, a decrease in small HDL particles was seen. Changes in VLDL and chylomicron particles in both groups and triglycerides and small HDL particles in the LPV group were statistically significant.
  
  
  CONCLUSIONS
  In HIV-type-1-positive men initiating antiretroviral therapy with FPV- or LPV-based regimens, there were no significant changes in whole-body insulin sensitivity after 2 weeks. A proatherogenic lipid profile characterized by increases in triglycerides, VLDL and chylomicron particles and LDL particles, and a decrease in small HDL particles, was observed in both groups.
authors.affiliation: HIV and Genitourinary Medicine, Chelsea and Westminster Hospital, London, UK. Paul.Randell@stgeorges.nhs.uk
authors.forename: Paul A
authors.initials: PA
authors.lastname: Randell
authors.forename: Akil G
authors.initials: AG
authors.lastname: Jackson
authors.forename: Marta
authors.initials: M
authors.lastname: Boffito
authors.forename: David J
authors.initials: DJ
authors.lastname: Back
authors.forename: John F
authors.initials: JF
authors.lastname: Tjia
authors.forename: Jessica
authors.initials: J
authors.lastname: Taylor
authors.forename: Sundhiya
authors.initials: S
authors.lastname: Mandalia
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Moyle
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D000273:Adipose Tissue / Q000187:drug effects; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002219:Carbamates / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016001:Confidence Intervals; D004334:Drug Administration Schedule; D004338:Drug Combinations; D050171:Dyslipidemias / Q000139:chemically induced; D005663:Furans; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D019259:Lamivudine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D008055:Lipids / Q000097:blood*; D061466:Lopinavir; D008297:Male; D010755:Organophosphates / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D063065:Organophosphonates / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D011744:Pyrimidinones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D019438:Ritonavir / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D013449:Sulfonamides / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D001786:Blood Glucose; D002219:Carbamates; D004338:Drug Combinations; D005663:Furans; D007328:Insulin; D008055:Lipids; D010755:Organophosphates; D063065:Organophosphonates; D011744:Pyrimidinones; D013449:Sulfonamides; D061466:Lopinavir; D019259:Lamivudine; D000068698:Tenofovir; D000225:Adenine; D019438:Ritonavir; C426859:fosamprenavir