Dolutegravir versus placebo in subjects harbouring HIV-1 with integrase inhibitor resistance associated substitutions: 48-week results from VIKING-4, a randomized study

Antivir Ther. 2015;20(3):343-8. doi: 10.3851/IMP2878. Epub 2014 Oct 16.


Background: The Phase III VIKING-3 study demonstrated that dolutegravir (DTG) 50 mg twice daily was efficacious in antiretroviral therapy (ART)-experienced subjects harbouring raltegravir- and/or elvitegravir-resistant HIV-1. VIKING-4 (ING116529) included a placebo-controlled 7-day monotherapy phase to demonstrate that short-term antiviral activity was attributable to DTG.

Methods: VIKING-4 is a Phase III randomized, double-blind study in therapy-experienced adults with integrase inhibitor (INI)-resistant virus randomized to DTG 50 mg twice daily or placebo while continuing their failing regimen (without raltegravir or elvitegravir) for 7 days ( identifier NCT01568892). At day 8, all subjects switched to open-label DTG 50 mg twice daily and optimized background therapy including ≥1 fully active drug. The primary end point was change from baseline in plasma HIV-1 RNA at day 8.

Results: The study population (n=30) was highly ART-experienced with advanced HIV disease. Patients had extensive baseline resistance to all approved antiretroviral classes. Adjusted mean change in HIV-1 RNA at day 8 was -1.06 log10 copies/ml for the DTG arm and 0.10 log10 copies/ml for the placebo arm (treatment difference -1.16 log10 copies/ml [-1.52, -0.80]; P<0.001). Overall, 47% and 57% of subjects had plasma HIV-1 RNA <50 and <400 copies/ml at week 24, and 40% and 53% at week 48, respectively. No discontinuations due to drug-related adverse events occurred in the study.

Conclusions: The observed day 8 antiviral activity in this highly treatment-experienced population with INI-resistant HIV-1 was attributable to DTG. Longer-term efficacy (after considering baseline ART resistance) and safety during the open-label phase were in-line with the results of the larger VIKING-3 study.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD4 Lymphocyte Count
  • Drug Resistance, Viral*
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV Integrase Inhibitors / pharmacology
  • HIV Integrase Inhibitors / therapeutic use*
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • Heterocyclic Compounds, 3-Ring / pharmacology
  • Heterocyclic Compounds, 3-Ring / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Oxazines
  • Piperazines
  • Pyridones
  • Treatment Outcome
  • Viral Load
  • Young Adult


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

Associated data