Tolerability of HIV integrase inhibitors

Curr Opin HIV AIDS. 2012 Sep;7(5):422-8. doi: 10.1097/COH.0b013e328356682a.


Purpose of review: This review discusses the available safety data for three integrase strand transfer inhibitors (INSTIs)--raltegravir, elvitegravir and dolutegravir--derived from studies in both HIV-infected and HIV-uninfected cohorts.

Recent findings: Phase 2 and 3 clinical trials show that all three INSTIs are well tolerated in treatment-naive and treatment-experienced patients with headache and gastrointestinal effects being the most commonly reported adverse events. Other nervous system (including neuropsychiatric) effects are often reported with INSTIs but are milder and less frequent than with efavirenz. Limited data suggest that effects upon lipid metabolism with raltegravir and dolutegravir are favourable compared with efavirenz and protease inhibitors, with more variable findings for elvitegravir because of coadministration with the boosting agent cobicistat. Cobicistat and dolutegravir have effects upon proximal renal tubular function causing mild-to-moderate creatinine elevation. Rare and severe events possibly related to INSTIs include systemic hypersensitivity reactions and rhabdomyolysis.

Summary: INSTIs are an important recent addition to the antiretroviral armamentarium, with good short-term and medium-term safety. Long-term data from ongoing clinical studies are needed for a definitive assessment of their safety profile.

Publication types

  • Review

MeSH terms

  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • HIV Infections / drug therapy*
  • HIV Integrase Inhibitors / administration & dosage*
  • HIV Integrase Inhibitors / adverse effects*
  • Heterocyclic Compounds, 3-Ring / administration & dosage
  • Heterocyclic Compounds, 3-Ring / adverse effects
  • Humans
  • Kidney / drug effects
  • Lipid Metabolism / drug effects
  • Oxazines
  • Piperazines
  • Pyridones
  • Pyrrolidinones / administration & dosage
  • Pyrrolidinones / adverse effects
  • Quinolones / administration & dosage
  • Quinolones / adverse effects
  • Raltegravir Potassium


  • HIV Integrase Inhibitors
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • Pyrrolidinones
  • Quinolones
  • Raltegravir Potassium
  • elvitegravir
  • dolutegravir