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NNRTI Non-nucleoside reverse transcriptase inhibitors

Mechanism of action

Bind a hydrophobic pocket close to (not in) the reverse transcriptase active site, causing an allosteric change that blocks DNA polymerisation. No intracellular activation is needed. Active against HIV-1 only (not HIV-2 or group O).

Genetic barrier to resistance

Low: a single mutation (e.g. K103N, Y181C, E138K) can confer high-level resistance.

Class effects to know

  • Rash (including severe cutaneous reactions)
  • Hepatotoxicity
  • CYP3A substrates or inducers — interaction-prone
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 NNRTI (reverse transcription).

Drugs in this class

Efavirenz (EFV) SmPC not downloaded Rilpivirine (RPV) SmPC not downloaded Doravirine (DOR) SmPC not downloaded Etravirine (ETR) SmPC not downloaded