Dolutegravir: a next-generation integrase inhibitor for treatment of HIV infection

Clin Infect Dis. 2014 Jul 15;59(2):265-71. doi: 10.1093/cid/ciu221. Epub 2014 Apr 9.

Abstract

Dolutegravir (DTG), a next-generation integrase strand transfer inhibitor (INSTI), was recently approved for use in the treatment of human immunodeficiency virus infection. In treatment-naive trial participants, DTG given at 50 mg once daily without pharmacologic boosting combined with a standard nucleoside backbone was shown to be noninferior or superior to first-line regimens containing efavirenz, darunavir/ritonavir, or raltegravir regardless of pretreatment viral load. This drug also exhibited efficacy in antiretroviral therapy-experienced participants and has proven to retain activity when dosed twice daily in some participants harboring resistance to the other INSTIs, raltegravir and elvitegravir. DTG has few drug interactions and is taken without regard to meals. It causes benign elevations in serum creatinine based on its inhibition of tubular creatinine secretion without affecting the glomerular filtration rate. Overall, DTG is well tolerated, with headache and insomnia being the most frequently reported adverse events.

Keywords: HIV; INSTI; dolutegravir; integrase; resistance.

Publication types

  • Review

MeSH terms

  • Antiretroviral Therapy, Highly Active / adverse effects
  • Antiretroviral Therapy, Highly Active / methods*
  • Clinical Trials as Topic
  • Creatinine / blood
  • Drug Interactions
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Glomerular Filtration Rate
  • HIV Infections / drug therapy*
  • HIV Integrase Inhibitors / adverse effects
  • HIV Integrase Inhibitors / therapeutic use*
  • Heterocyclic Compounds, 3-Ring / adverse effects
  • Heterocyclic Compounds, 3-Ring / therapeutic use*
  • Humans
  • Oxazines
  • Piperazines
  • Pyridones
  • Treatment Outcome

Substances

  • HIV Integrase Inhibitors
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • Creatinine
  • dolutegravir