title: Effect of dolutegravir functional monotherapy on HIV-1 virological response in integrase strand transfer inhibitor resistant patients.
abstract: VIKING-4 assessed the safety and efficacy of dolutegravir in heavily antiretroviral treatment-experienced patients who had documented integrase strand transfer inhibitor (INSTI) resistance-associated substitutions in their HIV. VIKING-4 had a placebo-controlled 7-day dolutegravir functional monotherapy phase followed by dolutegravir plus an optimized background regimen for 48 weeks.
  
  
  
  Independent resistance analyses evaluated week 48 virological responses in the VIKING-4 trial based on the presence of baseline INSTI resistance-associated substitutions and baseline dolutegravir phenotypic susceptibility. Response rates at week 48 based on baseline dolutegravir resistance subgroups were compared for the 7-day dolutegravir functional monotherapy arm and placebo-control arm. Additionally, genotypic and phenotypic resistance at day 8 and time of failure was analysed for the virological failures from both arms.
  
  
  
  Week 48 response rates for VIKING-4 were 23% (3/13) in the 7-day dolutegravir functional monotherapy arm compared with 60% (9/15) in the 7-day placebo arm. Response rates were consistently lower in the dolutegravir functional monotherapy arm across baseline INSTI genotypic and phenotypic subgroups. There was a higher proportion of virological failures in the 7-day dolutegravir functional monotherapy arm (n=6/13; 46%) compared with the 7-day placebo arm (n=3/15; 20%). Additionally, five virological failures in the dolutegravir arm had virus expressing emergent INSTI resistance-associated substitutions compared with two in the placebo arm.
  
  
  
  Analysis of response rates and resistance emergence in VIKING-4 suggests careful consideration should be given to the duration of functional monotherapy in future studies of highly treatment-experienced patients to reduce the risk of resistance and virological failure.
authors: Division of Antiviral Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
authors: Lisa K
authors: LK
authors: Naeger
authors: Division of Antiviral Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
authors: Patrick
authors: P
authors: Harrington
authors: Division of Antiviral Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
authors: Takashi
authors: T
authors: Komatsu
authors: Division of Antiviral Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
authors: Damon
authors: D
authors: Deming
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D019427:HIV Integrase / Q000235:genetics; D019428:HIV Integrase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006575:Heterocyclic Compounds, 3-Ring / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D017211:Treatment Failure; D000099226:Dolutegravir
chemical_list: D019427:HIV Integrase; D019428:HIV Integrase Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D000099226:Dolutegravir