Dolutegravir in antiretroviral-experienced patients with raltegravir- and/or elvitegravir-resistant HIV-1: 24-week results of the phase III VIKING-3 study

J Infect Dis. 2014 Aug 1;210(3):354-62. doi: 10.1093/infdis/jiu051. Epub 2014 Jan 19.

Abstract

Background: The pilot phase IIb VIKING study suggested that dolutegravir (DTG), a human immunodeficiency virus (HIV) integrase inhibitor (INI), would be efficacious in INI-resistant patients at the 50 mg twice daily (BID) dose.

Methods: VIKING-3 is a single-arm, open-label phase III study in which therapy-experienced adults with INI-resistant virus received DTG 50 mg BID while continuing their failing regimen (without raltegravir or elvitegravir) through day 7, after which the regimen was optimized with ≥1 fully active drug and DTG continued. The primary efficacy endpoints were the mean change from baseline in plasma HIV-1 RNA at day 8 and the proportion of subjects with HIV-1 RNA <50 c/mL at week 24.

Results: Mean change in HIV-1 RNA at day 8 was -1.43 log10 c/mL, and 69% of subjects achieved <50 c/mL at week 24. Multivariate analyses demonstrated a strong association between baseline DTG susceptibility and response. Response was most reduced in subjects with Q148 + ≥2 resistance-associated mutations. DTG 50 mg BID had a low (3%) discontinuation rate due to adverse events, similar to INI-naive subjects receiving DTG 50 mg once daily.

Conclusions: DTG 50 mg BID-based therapy was effective in this highly treatment-experienced population with INI-resistant virus.

Clinical trials registration: www.clinicaltrials.gov (NCT01328041) and http://www.gsk-clinicalstudywww.gsk-clinicalstudyregister.com (112574).

Keywords: DTG; dolutegravir; elvitegravir resistance; integrase inhibitor; raltegravir resistance.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use
  • Drug Resistance, Viral*
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • Heterocyclic Compounds, 3-Ring / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Oxazines
  • Pilot Projects
  • Piperazines
  • Pyridones
  • Pyrrolidinones / pharmacology*
  • Quinolones / pharmacology*
  • RNA, Viral / blood
  • Raltegravir Potassium
  • Viral Load

Substances

  • Anti-HIV Agents
  • Heterocyclic Compounds, 3-Ring
  • JTK 303
  • Oxazines
  • Piperazines
  • Pyridones
  • Pyrrolidinones
  • Quinolones
  • RNA, Viral
  • Raltegravir Potassium
  • dolutegravir

Associated data

  • ClinicalTrials.gov/NCT01328041