title: Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO): 96 week results from a randomised, open-label, phase 3b study.
abstract: BACKGROUND
  The primary analysis of the FLAMINGO study at 48 weeks showed that patients taking dolutegravir once daily had a significantly higher virological response rate than did those taking ritonavir-boosted darunavir once daily, with similar tolerability. We present secondary efficacy and safety results analysed at 96 weeks.
  
  
  METHODS
  FLAMINGO was a multicentre, open-label, phase 3b, non-inferiority study of HIV-1-infected treatment-naive adults. Patients were randomly assigned (1:1) to dolutegravir 50 mg or darunavir 800 mg plus ritonavir 100 mg, with investigator-selected combination tenofovir and emtricitabine or combination abacavir and lamivudine background treatment. The main endpoints were plasma HIV-1 RNA less than 50 copies per mL and safety. The non-inferiority margin was -12%. If the lower end of the 95% CI was greater than 0%, then we concluded that dolutegravir was superior to ritonavir-boosted darunavir. This trial is registered with ClinicalTrials.gov, number NCT01449929.
  
  
  RESULTS
  Of 595 patients screened, 488 were randomly assigned and 484 included in the analysis (242 assigned to receive dolutegravir and 242 assigned to receive ritonavir-boosted darunavir). At 96 weeks, 194 (80%) of 242 patients in the dolutegravir group and 164 (68%) of 242 in the ritonavir-boosted darunavir group had HIV-1 RNA less than 50 copies per mL (adjusted difference 12·4, 95% CI 4·7-20·2; p=0·002), with the greatest difference in patients with high viral load at baseline (50/61 [82%] vs 32/61 [52%], homogeneity test p=0·014). Six participants (three since 48 weeks) in the dolutegravir group and 13 (four) in the darunavir plus ritonavir group discontinued because of adverse events. The most common drug-related adverse events were diarrhoea (23/242 [10%] in the dolutegravir group vs 57/242 [24%] in the darunavir plus ritonavir group), nausea (31/242 [13%] vs 34/242 [14%]), and headache (17/242 [7%] vs 12/242 [5%]).
  
  
  CONCLUSIONS
  Once-daily dolutegravir is associated with a higher virological response rate than is once-daily ritonavir-boosted darunavir. Dolutegravir compares favourably in efficacy and safety to a boosted darunavir regimen with nucleoside reverse transcriptase inhibitor background treatment for HIV-1-infected treatment-naive patients.
  
  
  BACKGROUND
  ViiV Healthcare and Shionogi & Co.
authors.affiliation: University of Paris Diderot Paris 7, Sorbonne Paris Cité, INSERM U941, Department of Infectious Diseases, Saint-Louis Hospital, Assistance Publique Hôpitaux de Paris, Paris, France. Electronic address: jean-michel.molina@sls.aphp.fr.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.affiliation: Hospital Universitari Germans Trias i Pujol, HIV Unit, Irsicaixa Foundation, UAB, UVIC-UCC, Badalona, Catalonia, Spain.
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.affiliation: University Medical Center Hamburg-Eppendorf, Infectious Diseases Unit, Hamburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: van Lunzen
authors.affiliation: IRCCS San Raffaele Via Stamira d'Ancona, Department of Infectious Diseases, Milan, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.affiliation: Lausanne University Hospital, Infectious Disease Service, Lausanne, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.affiliation: Hennepin County Medical Center, Department of Medicine, Minneapolis, MN, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Henry
authors.affiliation: Clinical Center for Prevention and Control of AIDS, Krasnodar, Russia.
authors.forename: Valeriv
authors.initials: V
authors.lastname: Kulagin
authors.affiliation: GlaxoSmithKline, Clinical Statistics, Stockley Park, UK.
authors.forename: Naomi
authors.initials: N
authors.lastname: Givens
authors.affiliation: PPD, Pharmacovigilance, Morrisville, NC, USA.
authors.forename: Carlos Fernando
authors.initials: CF
authors.lastname: de Oliveira
authors.affiliation: GlaxoSmithKline, Infectious Diseases, Research Triangle Park, NC, USA.
authors.forename: Clare
authors.initials: C
authors.lastname: Brennan
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D000069454:Darunavir / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000187:drug effects*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D015497:HIV-1; D006575:Heterocyclic Compounds, 3-Ring / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D019438:Ritonavir / Q000008:administration & dosage*; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects*; D000099226:Dolutegravir
chemical_list: D019380:Anti-HIV Agents; D000069454:Darunavir; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D019438:Ritonavir; D000099226:Dolutegravir