Effect of boosted fosamprenavir or lopinavir-based combinations on whole-body insulin sensitivity and lipids in treatment-naive HIV-type-1-positive men

• Published in: Antiviral therapy 2010-01, Vol.15 (8), p.1125-1132
• Main Authors: RANDELL, Paul A, JACKSON, Akil G, BOFFITO, Marta, BACK, David J, TJIA, John F, TAYLOR, Jessica, MANDALIA, Sundhiya, MOYLE, Graeme J
• Format: Article
• Language: English
• Subjects: Adenine - adverse effects; Adenine - analogs & derivatives; Adenine - pharmacokinetics; Adenine - therapeutic use; Adipose Tissue - drug effects; Adult; Anti-HIV Agents - adverse effects; Anti-HIV Agents - pharmacokinetics; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Blood Glucose - drug effects; Blood Glucose - metabolism; Carbamates - adverse effects; Carbamates - pharmacokinetics; Carbamates - therapeutic use; Confidence Intervals; Drug Administration Schedule; Drug Combinations; Dyslipidemias - chemically induced; HIV Infections - complications; HIV Infections - drug therapy; HIV Infections - metabolism; HIV-1; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Insulin - blood; Insulin Resistance - physiology; Lamivudine - adverse effects; Lamivudine - pharmacokinetics; Lamivudine - therapeutic use; Lipids - blood; Lopinavir; Male; Medical sciences; Organophosphates - adverse effects; Organophosphates - pharmacokinetics; Organophosphates - therapeutic use; Organophosphonates - adverse effects; Organophosphonates - pharmacokinetics; Organophosphonates - therapeutic use; Pharmacology. Drug treatments; Pyrimidinones - adverse effects; Pyrimidinones - pharmacokinetics; Pyrimidinones - therapeutic use; Ritonavir - adverse effects; Ritonavir - pharmacokinetics; Ritonavir - therapeutic use; Sulfonamides - adverse effects; Sulfonamides - pharmacokinetics; Sulfonamides - therapeutic use; Tenofovir; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 1359-6535; 2040-2058
• DOI: 10.3851/IMP1675

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. 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. 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. 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.