Clinical trials on the safety and efficacy of fosamprenavir in HAART-naive HIV-1 infected patients have been extensively published.

The NEAT Trial

The NEAT study was a 48-week, multi-center, open-label comparative study. To evaluate the safety and efficacy of fos-amprenavir versus nelfinavir (Viracept®, Agouron), investigators enrolled 249 HAART-naive adults with a plasma HIV-1/RNA of 5,000 or more copies/ml at screening. In a 2:1 ratio, patients were assigned either fosamprenavir or nelfin-avir for a minimum of 48 weeks in addition and lamividine.

In 166 patients receiving fosamprenavir (1,400 mg twice daily), 66%—compared with 51% of the 83 patients taking nelfinavir (1,250 mg twice daily) — achieved a viral load below 400 copies/ ml. Furthermore, 55% of the patients receiving fosamprenavir achieved a viral load of fewer than 50 copies/ml, compared with 41% of the nelfinavir patients. The percentage of patients experiencing virological failure was higher in the nel-finavir group (28%) than in the fosam-prenavir group (14%). In both groups, the incidence of dose-limiting ADEs and laboratory abnormalities was insignificant, except for diarrhea, which was more common in the nelfinavir group (18%) than in the fosamprenavir group (5%).

The SOLO Trial

The SOLO trial evaluated the safety and efficacy of fosamprenavir boosted with ritonavir (Abbott) versus nelfinavir for 48 weeks. In this open-label study, 649 HAART-naive patients were randomly selected, in a 1:1 ratio, to receive fosamprenavir 1,400 mg/riton-avir 200 mg daily or nelfinavir 1,250 mg twice daily in combination with abacavir. The results revealed comparable efficacy; 68% of patients receiving the combination and 65% of those receiving nelfinavir achieved an undetectable HIV-1/RNA level (fewer than 400 copies/ml). Fifty-six percent of the fosamprenavir/ritonavir patients, compared with 52% of the nelfinavir patients, achieved a viral load below 50 copies/ml. Although no discernible differences in efficacy and tolerability were seen among the groups, the results of this study confirmed the added benefit of a low pill burden.

The CONTEXT Trial

CONTEXT, a phase III, randomized, open-label, non-inferiority study, was conducted to compare the antiviral response of patients receiving two different dosing regimens of boosted fosamprenavir with that of patients receiving lopinavir/ ritonavir (Kaletra®, Abbott) at 24 and 48 weeks, respectively. The primary end-point of the trial was the mean time average change in plasma HIV-1/RNA levels at baseline to week 24 in 315 PI-experienced patients. For all of the patients, therapy had been unsuccessful with their current regimen.

The patients were randomly selected, in a 1:1:1 ratio, to receive fosamprenavir 1,400 mg/ritonavir 200 mg once daily, fosamprenavir 700 mg twice daily, or lopinavir 400 mg/riton-avir 100 mg twice daily in combination with two nucleoside reverse transcrip-tase inhibitors (NRTIs) that were selected on the basis of resistance testing. From the baseline evaluation to week 24, the time-averaged changes in HIV-1/ RNA were -1.46 log10 copies/ml for the fosamprenavir/ritonavir once-daily arm, -1.48 log10 copies/ml for the fosam-prenavir/ritonavir twice-daily arm, and -1.63 log10 copies/ml for the lopinavir/ ritonavir twice-daily arm. The median CD4 cells/mm3 changes from baseline were 72 for once-daily fosamprenavir/ ritonavir, 62 for twice-daily fosampren-avir/ritonavir, and 63 for twice-daily lopinavir/ritonavir. Thus, after 24 weeks, the investigators concluded that boosted fosamprenavir was equivalent to lopinavir/ritonavir.