As with all other anti-HIV drugs, strains of HIV that are resistant to fosamprenavir (Telzir) may emerge after a period of treatment. The emergence of drug-resistant strains coincides with a fall in the effectiveness of the drug.

As fosamprenavir is a pro-drug of amprenavir (Agenerase), it is susceptible to the same mutations as amprenavir, although clinical studies have found that ritonavir boosting lowers the rate of resistance emergence.

The main mutation associated with amprenavir resistance is I50V. There is evidence to suggest that this mutation is unique to amprenavir and fosamprenavir. Consequently, people with resistance to other protease inhibitors may benefit from the use of fosamprenavir, although I50V may reduce the response to lopinavir. Other mutations associated with fosamprenavir resistance include^[1]:

• V32I.
• M46I/L, which reduces sensitivity to all protease inhibitors except for saquinavir (Invirase)^[2].
• I47V^[3].
• I54L/M.
• I84V, which confers resistance to all available protease inhibitors.
• L90M, which causes resistance to saquinavir and nelfinavir (Viracept).