The present invention provides methods and devices for predicting whether an HIV-I is likely to have a reduced susceptibility to an antiviral drug based on the HIV-I's genotype. In one aspect, the invention provides methods comprising determining whether a mutation or combination of mutations associated with altered susceptibility to protease inhibitors are present, as disclosed herein, thereby assessing the effectiveness of tipranavir therapy in the HIV-infected subject. Computer implemented methods comprising determining HIV-I's altered susceptibility are provided.