title: Safety and efficacy of dolutegravir in treatment-experienced subjects with raltegravir-resistant HIV type 1 infection: 24-week results of the VIKING Study.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Infectious Diseases Division, School of Medicine, University of North Carolina, Chapel Hill, NC 27599-7215, USA. jeron@med.unc.edu
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Eron
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Jacques
authors.initials: J
authors.lastname: Durant
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.forename: Princy
authors.initials: P
authors.lastname: Kumar
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.forename: Isabelle
authors.initials: I
authors.lastname: Poizot-Martin
authors.forename: Gary
authors.initials: G
authors.lastname: Richmond
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
authors.forename: Mounir
authors.initials: M
authors.lastname: Ait-Khaled
authors.forename: Tamio
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Jenny
authors.initials: J
authors.lastname: Huang
authors.forename: Sherene
authors.initials: S
authors.lastname: Min
authors.forename: Cindy
authors.initials: C
authors.lastname: Vavro
authors.forename: Jane
authors.initials: J
authors.lastname: Yeo
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000494:pharmacology; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification; D006575:Heterocyclic Compounds, 3-Ring / Q000008:administration & dosage* / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010078:Oxazines; D010865:Pilot Projects; D010879:Piperazines; D010949:Plasma / Q000821:virology; D011728:Pyridones; D011760:Pyrrolidinones / Q000494:pharmacology*; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult; D000099226:Dolutegravir
chemical_list: D019380:Anti-HIV Agents; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D011760:Pyrrolidinones; D012367:RNA, Viral; D000068898:Raltegravir Potassium; D000099226:Dolutegravir