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Lancet HIV. 2015 Apr;2(4):e127-36. doi: 10.1016/S2352-3018(15)00027-2. Epub 2015 Mar 10.

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.

Author information

1
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.
2
Hospital Universitari Germans Trias i Pujol, HIV Unit, Irsicaixa Foundation, UAB, UVIC-UCC, Badalona, Catalonia, Spain.
3
University Medical Center Hamburg-Eppendorf, Infectious Diseases Unit, Hamburg, Germany.
4
IRCCS San Raffaele Via Stamira d'Ancona, Department of Infectious Diseases, Milan, Italy.
5
Lausanne University Hospital, Infectious Disease Service, Lausanne, Switzerland.
6
Hennepin County Medical Center, Department of Medicine, Minneapolis, MN, USA.
7
Clinical Center for Prevention and Control of AIDS, Krasnodar, Russia.
8
GlaxoSmithKline, Clinical Statistics, Stockley Park, UK.
9
PPD, Pharmacovigilance, Morrisville, NC, USA.
10
GlaxoSmithKline, Infectious Diseases, Research Triangle Park, NC, USA.

Erratum in

  • Lancet HIV. 2015 Apr;2(4):e126.

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.

FINDINGS:

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%]).

INTERPRETATION:

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.

FUNDING:

ViiV Healthcare and Shionogi & Co.

Comment in

PMID:
26424673
DOI:
10.1016/S2352-3018(15)00027-2
[Indexed for MEDLINE]

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