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INSTI Integrase strand-transfer inhibitors

Mechanism of action

Chelate the two Mg²⁺ ions in the integrase active site, blocking the strand-transfer step that inserts proviral DNA into the host genome.

Genetic barrier to resistance

High for dolutegravir and bictegravir; low for raltegravir and elvitegravir.

Class effects to know

  • Weight gain
  • Insomnia, headache, neuropsychiatric effects
  • Chelation by polyvalent cations (antacids, iron, calcium) lowers absorption
  • Dolutegravir and bictegravir inhibit OCT2 → small, non-progressive creatinine rise
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 INSTI (integration).

Drugs in this class

Dolutegravir (DTG) SmPC not downloaded Bictegravir (BIC) SmPC not downloaded Raltegravir (RAL) SmPC not downloaded Cabotegravir (CAB) SmPC not downloaded