An Update on HIV-1 Protease Inhibitor Resistance

Protease inhibitors (PIs) were initially introduced in the mid-1990s and when used in combination with nucleoside reverse transcriptase inhibitors (NRTI), ushered in the era of highly active antiretroviral therapy (HAART). These agents dramatically altered the treatment of HIV infection, enabling suppression of viral replication to undetectable levels and significantly impacting disease progression and mortality. However, HIV-1 drug resistance has been observed with all the PIs and the genetic basis of resistance has been well described [1]. The accumulation of multiple mutations is often required to produce PI resistance and there is variability of resistance patterns within the PI class. Some PIs require fewer mutations to confer resistance compared with others. In addition, the development of broad cross-resistance to multiple agents in this class presents a challenge in clinical practice.