What causes resistance to second-generation protease inhibitors in antiretroviral therapy of HIV infection?

Updated: Apr 18, 2019
  • Author: R Chris Rathbun, PharmD, BCPS (AQ-ID), AAHIVP; Chief Editor: John Bartlett, MD  more...
  • Print


The second-generation protease inhibitors lopinavir/ritonavir, darunavir, and tipranavir may retain activity in the presence of resistance to first-generation agents. Lopinavir/ritonavir requires the accumulation of 7 or more mutations before high-level resistance develops. [43] Darunavir and tipranavir typically retain activity against lopinavir/ritonavir and first-generation protease inhibitor–resistant strains. [43]

Eleven resistance mutations have been described for darunavir; accumulation of 3 or more is associated with virologic failure. Tipranavir also requires accumulation of multiple nonoverlapping mutations before high-level resistance develops. [43]

A review of 2725 HIV isolates for protease inhibitor susceptibility revealed that certain mutations could result in increased susceptibility to a particular drug, and that some effects on resistance had been underestimated. [45] The study concluded that cross-resistance between the various protease inhibitors now and in the future may be missed without systematic analysis of the effects of specific mutations.

Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!