The recent SOLO clinical trial demonstrated that the efficacy at 48 weeks of HAART regimens containing fosamprenavir/ritonavir vs. nelfinavir in treatment-naïve patients was similar. However, relative cost comparisons of the two regimens have not been evaluated in light of the 400% price increase of ritonavir. OBJECTIVES: A cost comparison analysis was conducted of HAART regimens fosamprenavir/ritonavir vs. nelfinavir. METHODS: Clinical efficacy and dosing parameters were extracted from the SOLO trial and package inserts. Although recommendations dictate twice daily dosing regimens for protease inhibitors, the baseline assumption for treatment-naïve patients was the recommended 1400/200 mg once daily dosing regimen. The efficacy of nelfinavir 250 mg and 650 mg was assumed to be identical. Sensitivity analysis was conducted on cost of therapy and cost savings for different scenarios of average wholesale price (AWP), discounts from the AWP, and number of tablets per day. Daily, monthly, and 48-week costs of nelfinavir versus ritonavir-boosted fosamprenavir were compared. RESULTS: Due to the price change in ritonavir, the drug acquisition cost per day of fosamprenavir boosted with ritonavir increased 73% from $23.48 to $40.71. The nelfinavir 625 mg twice daily dosing regimen resulted in monthly cost savings of $502 and a 48-week cost-reduction of $5545 (41%) compared to fosamprenavir/ritonavir 1400/200 mg once daily regimen. A discount of approximately 75% on the ritonavir AWP would make the drug acquisition cost of fosamprenavir boosted with ritonavir equal to that of nelfinavir. CONCLUSION: The price increase of ritonavir significantly affects drug acquisition cost for patients taking fosamprenavir and other boosted protease inhibitors. Without compromising clinical efficacy, nelfinavir provides a cost-saving alternative for treatment-naïve HIV-infected patients compared to ritonavir-boosted fosamprenavir.