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Resistance and cross-resistance with saquinavir and other HIV protease inhibitors: theory and practice.

The addition of the HIV protease inhibitors to the growing list of antiretrovirals, and the increasing acceptance of polypharmacy in the treatment of HIV infection, has resulted in a marked improvement in clinical response to therapy such that commentators are optimistically suggesting that HIV infection may soon be regarded as a treatable chronic infection. Indeed, with 10 or more drugs now available or imminent, several consecutive double or triple therapy regimens can be used, employing a completely new set of agents at each change. This strategy could potentially provide several years of successful therapy, during which time additional drugs may well become available to provide ongoing treatment. In order to optimize the sequential use of the available drugs, it is important to sequence them in such a way as to minimize the risk of drugs used early in treatment restricting the subsequent use of the related drugs by the induction of cross-resistance. Thus, an understanding of the factors involved in the emergence of viral drug resistance and cross-resistance will help the design of individual treatment regimens with potential long-term value.