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Published on: April 9, 2014

Novel mechanisms of HIV protease inhibitor resistance

Monique Nijhuis1, Noortje M van Maarseveen, Jens Verheyen

  • 1Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.

Current Opinion in HIV and AIDS
|April 18, 2009
PubMed
Abstract

Insights

Protease inhibitor resistance can arise from various mechanisms. Currently, only changes in protease cleavage sites are linked to reduced drug effectiveness and treatment failure.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Virology

Background:

  • Protease inhibitors are crucial in treating viral infections.
  • Understanding resistance mechanisms is key to effective therapy.
  • Several pathways for protease inhibitor resistance have been hypothesized.

Purpose of the Study:

  • To review proposed mechanisms of protease inhibitor resistance.
  • To assess the clinical relevance of these resistance mechanisms.

Main Methods:

  • Literature review of proposed protease inhibitor resistance mechanisms.
  • Analysis of studies investigating the clinical impact of resistance.

Main Results:

  • Only alterations in protease cleavage sites, with or without accompanying protease mutations, correlate with changes in IC50 (in vitro drug susceptibility) and virological failure.
  • Other proposed resistance mechanisms lack definitive clinical validation.

Conclusions:

  • Cleavage site alterations are currently the only established mechanism driving protease inhibitor resistance with clinical consequences.
  • Further research is needed to elucidate the precise mechanisms, clinical significance, and transmission dynamics of cleavage site changes.

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