Switching to unboosted atazanavir improves glucose tolerance in highly pretreated HIV-1 infected subjects

• Published in: European journal of endocrinology Vol. 156; no. 4; pp. 503 - 509
• Main Authors: Guffanti, Monica, Caumo, Andrea, Galli, Laura, Bigoloni, Alba, Galli, Andrea, Dagba, Geneviéve, Danise, Anna, Luzi, Livio, Lazzarin, Adriano, Castagna, Antonella
• Format: Journal Article
• Language: English
• Published: Colchester European Society of Endocrinology 01.04.2007; Portland Press
• Subjects: Adult; Atazanavir Sulfate; Biological and medical sciences; Blood Glucose - metabolism; Clinical Studies; Endocrinopathies; Fasting - blood; Fasting - metabolism; Female; Fundamental and applied biological sciences. Psychology; Glucose Tolerance Test; HIV Infections - blood; HIV Infections - drug therapy; HIV Protease Inhibitors - adverse effects; HIV Protease Inhibitors - therapeutic use; HIV-1; Human immunodeficiency virus 1; Humans; Lipid Metabolism; Male; Medical sciences; Middle Aged; Oligopeptides - adverse effects; Oligopeptides - therapeutic use; Pilot Projects; Prospective Studies; Protease Inhibitors - therapeutic use; Pyridines - adverse effects; Pyridines - therapeutic use; Retreatment; Treatment Outcome; Vertebrates: endocrinology; Immunopathology; Atazanavir; Enzyme; Enzyme inhibitor; Tolerance; AIDS; Glucose; Immune deficiency; Switching; Infection; Peptidases; Viral disease; Hydrolases; Protease inhibitor; Endocrinology
• ISSN: 0804-4643; 1479-683X
• DOI: 10.1530/EJE-06-0648

Objective: To evaluate the 24-week effects on glucose tolerance of switching from a protease inhibitor (PI)-based to an unboosted atazanavir-including regimen in highly pretreated HIV-1 infected subjects with metabolic alterations. Design: Prospective, open-label, single-center, 24-week pilot study. Methods: Twenty-one subjects underwent an oral glucose tolerance test (OGTT) at baseline (BL) and after 24 weeks of unboosted atazanavir. Insulin sensitivity and β-cell responsiveness were evaluated on the basis of static and dynamic data; fasting glucose, insulin, C-peptide, triglycerides (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), TC/HDL-c ratio, CD4+ cell count and HIV-1 RNA were measured. Results: After 24 weeks of unboosted atazanavir, the 120-min glucose level was significantly lower than the one measured at BL (P=0.021); there were no statistically significant differences in the insulin concentration profile. The SIoral, an OGTT-based index of insulin sensitivity, was significantly higher at week 24 (P=0.017); the indices of first- and second-phase β-cell responsiveness did not significantly change. There was no significant difference between BL and 24-week fasting glucose, insulin or C-peptide levels, and consequently no change in fasting homeostasis model assessment indices of insulin sensitivity and β-cell function. There were significant improvements in TG (P=0.009), TC (P=0.0001), LDL-c (P=0.019) and TC/HDL-c ratio (P=0.001), and a similar trend in HDL-c levels (P=0.069). No significant changes in the immunological and virological parameters were detected. Conclusions: Our results show that switching from a PI-based to an unboosted atazanavir-including regimen leads to a significant improvement in glucose tolerance in highly pretreated HIV-1 infected subjects with metabolic alterations.