In absence of previous treatments on PI's and based on the usual mutations that appear is there a "more logical order" when beginning a PI based treatment? (I'm speaking OF 908, KALETRA,REYATAZ)

This is a good question and one that can ignite quite a debate among HIV experts. My own thinking on this reflects the unique ability of ritonavir boosted PIs to be not only potent but also to be able to reduce the risk of PI resistance, even in those failing regimens that they are part of. In study after study of boosted PIs we see few people experiencing virologic failure. And, of those that do, typically none have PI resistance detected.

So, I feel, generally, one should start with the boosted PI that is likely to be best tolerated and adhered to and that there is little evidence to suggest an optimal sequence of PIs when boosted.

Whether to ever use atazanavir unboosted with ritonavir is a realted issue as resistance to this PI can be expected if failure ensures. In this case, you would need a potent salvage PI (Kaletra, tipranavir, TMC114) next. I do have patients for who unboosted atazanavir is ideal (bad lipid or diabetes problems, intolerance of ritonavir). Recall, atazanavir can not be taken without ritonavir in people also on tenofovir (due to drug interactions leading to reduced atazanavir levels) or on H2 blockers or drugs like Nexium.

DW