Safety and efficacy of dolutegravir in treatment-experienced subjects with raltegravir-resistant HIV type 1 infection: 24-week results of the VIKING Study

J Infect Dis. 2013 Mar 1;207(5):740-8. doi: 10.1093/infdis/jis750. Epub 2012 Dec 7.


Background: Dolutegravir (DTG; S/GSK1349572), a human immunodeficiency virus type 1 (HIV-1) integrase inhibitor, has limited cross-resistance to raltegravir (RAL) and elvitegravir in vitro. This phase IIb study assessed the activity of DTG in HIV-1-infected subjects with genotypic evidence of RAL resistance.

Methods: Subjects received DTG 50 mg once daily (cohort I) or 50 mg twice daily (cohort II) while continuing a failing regimen (without RAL) through day 10, after which the background regimen was optimized, when feasible, for cohort I, and at least 1 fully active drug was mandated for cohort II. The primary efficacy end point was the proportion of subjects on day 11 in whom the plasma HIV-1 RNA load decreased by ≥0.7 log(10) copies/mL from baseline or was <400 copies/mL.

Results: A rapid antiviral response was observed. More subjects achieved the primary end point in cohort II (23 of 24 [96%]), compared with cohort I (21 of 27 [78%]) at day 11. At week 24, 41% and 75% of subjects had an HIV-1 RNA load of <50 copies/mL in cohorts I and II, respectively. Further integrase genotypic evolution was uncommon. Dolutegravir had a good, similar safety profile with each dosing regimen.

Conclusion: Dolutegravir 50 mg twice daily with an optimized background provided greater and more durable benefit than the once-daily regimen. These data are the first clinical demonstration of the activity of any integrase inhibitor in subjects with HIV-1 resistant to RAL.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / pharmacology
  • Antiretroviral Therapy, Highly Active / methods
  • Drug Resistance, Viral*
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / drug effects
  • HIV-1 / isolation & purification
  • Heterocyclic Compounds, 3-Ring / administration & dosage*
  • Heterocyclic Compounds, 3-Ring / adverse effects*
  • Heterocyclic Compounds, 3-Ring / pharmacology
  • Humans
  • Male
  • Middle Aged
  • Oxazines
  • Pilot Projects
  • Piperazines
  • Plasma / virology
  • Pyridones
  • Pyrrolidinones / pharmacology*
  • RNA, Viral / blood
  • Raltegravir Potassium
  • Treatment Outcome
  • Viral Load
  • Young Adult


  • Anti-HIV Agents
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • Pyrrolidinones
  • RNA, Viral
  • Raltegravir Potassium
  • dolutegravir