Changes in lipid profiles after switching to a protease inhibitor-containing cART - unfavourable effect of fosamprenavir in obese patients

Objective One focus in the medical care of HIV-infected patients today is cardiovascular risk reduction. Metabolic disturbances occur frequently in patients taking protease inhibitors (PI) and are a major risk factor for atherosclerosis. With few published head-to head studies substance-specific differences concerning metabolic effects are insufficiently defined. Therefore this cohort study directly compared the metabolic profiles of boosted atazanavir (ATV/r), fosamprenavir (FPV/r) and saquinavir (SQV/r). Methods Data from a cohort of 124 HIV patients initiating a boosted regimen with one of the PIs at the University of Munich (LMU) infectious diseases outpatient clinic were retrospectively analyzed. The main outcome measures were median absolute total cholesterol levels and median relative change of total cholesterol levels after six months of PI-therapy. A multivariate linear regression model was built to identify and control for potential confounders of the association between PI-therapy and serum cholesterol level. Results 84 patients were treated with ATV/r, 23 patients received FPV/r and 17 patients SQV/r. Demographically the cohort constituted a representative sample of HIV-infected patients in Germany. There were no statistically significant differences between the comparison groups at baseline. After six months of therapy median serum cholesterol in the ATV/r group dropped significantly from 204 mg/dl to 186 mg/dl, while in the FPV/r and SQV/r groups a rise in serum cholesterol levels was observed from 179 mg/dl to 204 mg/dl and from 173 mg/ddl to 209 mg/dl respectively. The multivariate linear regression model identified a significant interaction between BMI at baseline and treatment with FPV/r: patients with higher BMI showed more prominent increases in serum cholesterol while taking FPV/r compared to patients with lower BMI. Conclusion This cohort study demonstrated the most favourable impact on serum cholesterol levels and thus cardiovascular risk for ATV/r compared to FPV/r and SQV/r under real-life conditions. Given the statistical interaction detected between FPV/r and BMI further studies assessing metabolic profiles of different antiretroviral drugs in specific patient populations are urgently needed.