Similar Virologic and Immunologic Efficacy With Fosamprenavir Boosted With 100 mg or 200 mg of Ritonavir in HIV-Infected Patients: Results of the LESS Trial

Purpose: Ritonavir (RTV) effectively boosts most protease inhibitors but is associated with significant dose-dependent adverse events (AEs). In an effort to better manage toxicities through a reduced dose of RN, this study compared fosamprenavir (FPV) boosted with RN 100 mg (FPV/r100) or with RN 200 mg (FPV/r200) daily. Methods: This 24-week, open-label study enrolled patients taking a FPV/r200-containing regimen who had HIV RNA <400 copies/mL and randomized them 1:2 to continue that regimen or simplify to FPV/r100 once daily. Other medications were not altered. The primary endpoint was the percentage of patients without suspected or confirmed virologic failure (HIV RNA >= 400 copies/mL) through week 24 by a missing/discontinuation equals failure (M/D=F) analysis. Noninferiority criteria were demonstrated if the lower bound of the 95% confidence interval (CI) for the difference in the primary endpoint rates between groups was greater than -12. Results: The 2 regimens met prespecified noninferiority criteria (FPV/r100, 92%; FPV/r200, 94%; 95% CI, -9.36 to 5.12). At week 24, the percentage of patients with HIV RNA <50 copies/mL by M/D=F was 83% in the FPV/r100 group and 85% in the FPV/r200 group. Drug-related grade 2-4 AEs were uncommon (FPV/r100, 4%; FPV/r200, 7%). Median changes in lipids were similar in both groups, with the exception of triglycerides (FPV/r100, -21 mg/dL; FPV/r200, -2 mg/dL). Conclusions: This 24-week study demonstrated that among previously suppressed patients, once-daily FPV/r100 was similar to FPV/r200 in virologic and immunologic effects but was associated with greater decreases from baseline in triglyceride levels.