Prospects for the Resistance to HIV Protease Inhibitors: Current Drug Design Approaches and Perspectives

One of the major challenges raised by HIV chemotherapy is the insurgence of viral resistance to drugs. Resistance to antiviral therapy has been observed for each of the different classes of anti-viral drugs: nucleoside reversetranscriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors. The crucial question for AIDS drug research community is: Should we continue the search of new anti-HIV drugs which can overcome HIV resistance insurgence or should we consider resistance to anti-HIV drugs as a futile challenge? This review, focussed specifically on HIV antiprotease drugs, highlights the different strategies which have been developed to design new anti-protease drugs which could overcome HIV resistance, and also reviews the different classes of compounds (peptidomimetic or non-peptidomimetic) actually under investigation in order to face the problem of HIV resistance to drug.