title: Dolutegravir versus placebo in subjects harbouring HIV-1 with integrase inhibitor resistance associated substitutions: 48-week results from VIKING-4, a randomized study.
abstract: 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 (clinicaltrials.gov 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.
authors.affiliation: Chelsea Village Medical, PC, New York, NY, USA.
authors.forename: Bisher
authors.initials: B
authors.lastname: Akil
authors.forename: Gary
authors.initials: G
authors.lastname: Blick
authors.forename: Debbie P
authors.initials: DP
authors.lastname: Hagins
authors.forename: Moti N
authors.initials: MN
authors.lastname: Ramgopal
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Richmond
authors.forename: Rafik M
authors.initials: RM
authors.lastname: Samuel
authors.forename: Naomi
authors.initials: N
authors.lastname: Givens
authors.forename: Cindy
authors.initials: C
authors.lastname: Vavro
authors.forename: Ivy H
authors.initials: IH
authors.lastname: Song
authors.forename: Brian
authors.initials: B
authors.lastname: Wynne
authors.forename: Mounir
authors.initials: M
authors.lastname: Ait-Khaled
mesh_terms: D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult; D000099226:Dolutegravir
chemical_list: D019428:HIV Integrase Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D000099226:Dolutegravir