Methods
We evaluated the PI cross-resistance in a cohort of HIV patients. Drug resistance interpretation was based on the  Stanford University beta test that assigns determined scores for each amino acid substitution (www.stanford.edu).

Results
Data from 246 patients were analyzed. Most of them were multi-PI experienced (SQV 62%, RTV 55%, IDV 73%, NFV 71%, APV and LPV 3%). There was a direct correlation (Pearson test P < 0.01) for all possible head to head comparisons of  resistance scores. However, we also observed a significant difference in the proportion of strains resistant to each PI: 84% to NFV, 64% to SQV, 56% to IDV or RTV, 51% to APV and 45% to LPV (P < 0.0001 for APV or LPV vs. other PIs). 22% and 34% of strains resistant to SQV were still susceptible to APV and LPV, respectively.  Similarly, 11% and 21% of strains resistant to IDV and RTV were still susceptible to APV or LPV and these values rose to 39% and 51% for NFV resistant strains. This last result was deeply influenced by the 15% of strains showing resistance to NFV mainly because of the presence of 30D/N mutation that were invariably susceptible to both APV and LPV.

Conclusions
The increment of resistance to one PI is associated to a progressive reduction of efficacy of all other drugs of this class. This intra-class cross-resistance is however not absolute and drugs such as APV and LPV can be effective on a quite large proportion of viruses resistant to other PIs. This is particularly true for viruses resistant to SQV and NFV.  This observation gives new insights on the possibility of PI sequencing.