Tipranavir (Aptivus) was developed as an alternative to existing protease inhibitors, which display a high level of cross-resistance. Test tube studies report that resistance to tipranavir is slow to develop, and that there is no clear pattern of cross-resistance to currently available protease inhibitors^[1][2].

One study reported that 90% of HIV isolates taken from people with high level resistance to indinavir (Crixivan), ritonavir (Norvir), nelfinavir (Viracept) or saquinavir (Invirase) were completely sensitive to tipranavir, while 8% were moderately resistant to tipranavir and 2% were highly resistant. While encouraging, this study indicates that there is some level of cross-resistance between tipranavir and the other protease inhibitors^[3].

In general, the clinical studies of tipranavir have found that the more protease inhibitor mutations a patient has, the less likely they are to experience a benefit of tipranavir treatment. However, patients with numerous protease inhibitor resistance mutations tend to have a better chance of virological suppression with tipranavir than with other protease inhibitors^[4].

Study BI 1182.52 found that having three or more protease inhibitor-associated mutations was associated with a poorer response to ritonavir-boosted tipranavir^[5][6][7]. Two other studies have looked at susceptibility to tipranavir in treatment-experienced people, finding that one or two universal protease inhibitor-associated mutations (at positions 33, 82, 84 or 90) decreased susceptibility to currently available protease inhibitors, but more than two of these mutations were required for reduced susceptibility to tipranavir^[8].

Tipranavir requires the accumulation of multiple protease mutations for decreased susceptibility to the drug. Over 17 separate resistance mutations have been identified, including I13L/V, E35D, N37D, D60E and A71T, a number of which have not been associated with resistance to any other protease inhibitors^[9].