Pharmacology of HIV integrase inhibitors

Curr Opin HIV AIDS. 2012 Sep;7(5):390-400. doi: 10.1097/COH.0b013e328356e91c.


Purpose of review: The purpose of this study is to review recent and relevant pharmacology data for three HIV integrase inhibitors: raltegravir (marketed), dolutegravir, and elvitegravir (both in phase III drug development).

Recent findings: Data from January 2011 to April 2012 were evaluated. These data better characterized integrase inhibitor pharmacokinetics, assessed dosing regimens, and investigated previously undescribed drug-drug interactions. Due to formulation challenges, raltegravir inter-patient and intra-patient pharmacokinetic variability is high. Twice-daily 400 mg dosing has been shown to be clinically superior to 800 mg once-daily dosing. A pediatric formulation of raltegravir with less variable pharmacokinetics and greater bioavailability was US Food and Drug Administration (US FDA)-approved in December 2011. Cobicistat-boosted elvitegravir, and the second-generation integrase inhibitor dolutegravir, have lower pharmacokinetic variability and are dosed once daily. Dolutegravir drug interactions are similar to raltegravir, whereas boosted elvitegravir participates in additional CYP3A-mediated interactions.

Summary: Raltegravir's potent antiretroviral activity has resulted in widespread use in both treatment-naïve and experienced patients. Dolutegravir and cobicistat-boosted elvitegravir have some pharmacokinetic advantages. Pharmacokinetic data in special populations (pregnancy, pediatrics) to optimize dosing are still required.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • HIV Infections / drug therapy*
  • HIV Integrase Inhibitors / administration & dosage*
  • HIV Integrase Inhibitors / pharmacokinetics*
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • Heterocyclic Compounds, 3-Ring / administration & dosage
  • Heterocyclic Compounds, 3-Ring / pharmacokinetics
  • Humans
  • Oxazines
  • Piperazines
  • Pyridones
  • Pyrrolidinones / administration & dosage
  • Pyrrolidinones / pharmacokinetics
  • Quinolones / administration & dosage
  • Quinolones / pharmacokinetics
  • Raltegravir Potassium
  • United States


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