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NRTI Nucleoside/nucleotide reverse transcriptase inhibitors

Mechanism of action

Prodrugs phosphorylated by host-cell kinases to the active triphosphate (diphosphate for tenofovir). The active anabolite competes with the natural deoxynucleotide for HIV reverse transcriptase and, lacking a 3'-hydroxyl group, terminates the growing proviral DNA chain once incorporated.

Genetic barrier to resistance

Low for lamivudine/emtricitabine alone (M184V/I); higher for tenofovir (K65R).

Class effects to know

  • Mitochondrial toxicity (older thymidine analogues: lipoatrophy, lactic acidosis, myopathy)
  • Lamivudine, emtricitabine and tenofovir also suppress hepatitis B — stopping them can cause an HBV flare
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 NRTI (reverse transcription).

Drugs in this class

Tenofovir alafenamide (TAF) SmPC not downloaded Tenofovir disoproxil (TDF) SmPC not downloaded Emtricitabine (FTC) SmPC not downloaded Lamivudine (3TC) SmPC not downloaded Abacavir (ABC) SmPC not downloaded Zidovudine (AZT) SmPC not downloaded