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PI Protease inhibitors

Mechanism of action

Peptidomimetic inhibitors of the viral aspartyl protease, preventing cleavage of the Gag and Gag-Pol polyproteins so that new virions are immature and non-infectious. Given with a pharmacokinetic booster (ritonavir or cobicistat).

Genetic barrier to resistance

High when boosted: several mutations are needed for darunavir resistance.

Class effects to know

  • Gastrointestinal effects
  • Dyslipidaemia
  • Many CYP3A-mediated interactions (via the booster)
HIV-1 replication cycle and antiretroviral targets Seven steps from attachment to maturation, each labelled with the antiretroviral class that blocks it. CD4⁺ T cell Nucleus — host DNA provirus HIV virion new infectious virion Attachment & fusion gp120 binds CD4 then CCR5/CXCR4 Capsid transport & uncoating capsid docks at the nuclear pore Reverse transcription RNA → double-stranded DNA Integration integrase inserts provirus Transcription & translation host machinery makes viral RNA/protein Assembly & budding Gag/Gag-Pol at the membrane Maturation protease cleaves Gag-Pol Entry Capsid NRTI NNRTI INSTI Capsid PI

This class acts at the step labelled PI (maturation).

Drugs in this class

Darunavir (DRV) SmPC not downloaded Atazanavir (ATV) SmPC not downloaded